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Lopes CDF, Pinto KP, Ferreira CMA, de Souza JB, Lopes RT, Alves ATNN, Souza EM, Sassone LM, da Silva EJNL. The risk of osteonecrosis after apical patency during antiresorptive therapy in an animal model. Int Endod J 2025; 58:776-786. [PMID: 39904856 DOI: 10.1111/iej.14207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 01/22/2025] [Indexed: 02/06/2025]
Abstract
AIM To evaluate whether performing apical patency (AP) poses a risk for the development of osteonecrosis in rats treated with the antiresorptive drugs Zoledronic Acid (ZA) or Denosumab (DMAB). METHODOLOGY Forty-two male Wistar rats were divided into six groups according to the medication administered and whether apical patency was performed (n = 7): ZA, ZA-AP, DMAB, DMAB-AP, and the control groups CON and CON-AP. The ZA and ZA-AP groups received 0.125 mg/kg of ZA, while the DMAB and DMAB-AP groups received 0.25 mg/kg of DMAB, both administered via intraperitoneal injection twice a week for 4 weeks. One week after completing drug administration, endodontic access was performed on the distal occlusal fossa of the lower left first molars in all animals. AP was carried out in the distal canal of the ZA-AP, DMAB-AP, and CON-AP groups using a size 10 K-file with the aid of an electronic apex locator, extending beyond the apical foramen. In the other groups, the file was inserted up short of apex as determined by electronic apex locator measurement. Coronal sealing was performed and after 21 days, the animals were euthanized, and visual analysis, micro-CT, and histopathological assessments were conducted to evaluate the presence or absence of osteonecrosis. Statistical analysis was performed using frequency statistics and a GLM multivariate ANOVA model followed by Tukey's test with significance at p < .05. RESULTS None of the animals exhibited bone exposure or other clinical signs associated with medication-related osteonecrosis of the jaw. No cortical bone destruction, periosteal reaction, or bone sequestration was observed in the micro-CT or histopathological assessments. Medication significantly influenced some micro-CT parameters (p < .05), while the apical patency alone did not (p > .05). When interacting with medication*apical patency, the ZA-AP group showed a significantly lower percentage of bone volume and bone mineral density compared to the ZA group, a tendency not observed in DMAB groups (p < .05). CONCLUSIONS Apical patency in rats treated with zoledronic acid or denosumab did not cause osteonecrosis of the jaw, only micro-CT changes in bone microarchitecture that cannot be linked to osteonecrosis in zoledronic acid treated animals.
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Affiliation(s)
- Clara de Figueiredo Lopes
- Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Karem Paula Pinto
- Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Claudio Malizia Alves Ferreira
- Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Jenif Braga de Souza
- Laboratory of Experimental Surgery, School of Medical Sciences, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Ricardo Tadeu Lopes
- Nuclear Engineering Program, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | | | - Erick M Souza
- Departament of Endodontics, Maranhão Federal University (UFMA), São Luís, Maranhão, Brazil
| | - Luciana Moura Sassone
- Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Emmanuel João Nogueira Leal da Silva
- Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
- Departament of Endodontics, Grande Rio University (UNIGRANRIO), Rio de Janeiro, Brazil
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Conceição GSA, Pinto KP, Ferreira CMA, de Souza JB, Lopes RT, Coelho BP, Sassone LM, da Silva EJNL. Detrimental effects of chronic sugar-sweetened carbonated soft drink consumption on inflammatory response and the size of apical periodontitis: An animal-based study. Int Endod J 2025; 58:579-586. [PMID: 39815648 DOI: 10.1111/iej.14192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 12/16/2024] [Accepted: 12/30/2024] [Indexed: 01/18/2025]
Abstract
AIM This study aimed to evaluate the effects of chronic consumption of two sugar-sweetened carbonated soft drinks - one containing caffeine (Coca-Cola®) and one without (Sprite®) - on the progression of periapical lesions and the levels of pro-inflammatory cytokines in rats. METHODOLOGY Twelve Wistar rats were divided into three groups (n = 4): Control group, Coca-Cola group and Sprite group. The rats in Coca-Cola and Sprite groups were given ad libitum access to their respective soft drinks for 3 months, while the Control group received filtered water. After 2 months of consumption, the pulps of the lower left first molars were exposed for 28 days to induce periapical lesions. Following euthanasia, the jaws were removed, and the periapical lesions were assessed using micro-computed tomography imaging. Blood samples were collected to analyse the pro-inflammatory cytokines IL-1β, IL-6, IL-2, IL-17 and TNF-α via Luminex assay. Non-parametric data were analysed using the Kruskal-Wallis test followed by Dunn's test, while parametric data were analysed using one-way ANOVA followed by Tukey's test (p < 0.05). RESULTS Both the Coca-Cola and Sprite groups exhibited periapical lesions with significantly greater volume and diameter compared to the Control group (p < 0.05). Additionally, both soft drink groups had significantly higher levels of IL-1β, IL-6 and IL-2 compared to the Control group (p < 0.05). The Sprite group displayed significantly higher levels of IL-1β than the Coca-Cola group (p < 0.05), while the Coca-Cola group showed significantly elevated TNF-α levels compared to both the Control and Sprite groups (p < 0.05). No significant differences in IL-17 levels were observed among the groups (p > 0.05). CONCLUSIONS The chronic consumption of sugar-sweetened carbonated soft drinks, regardless of caffeine content, has detrimental effects on the inflammatory response and progression of apical periodontitis in rats.
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Affiliation(s)
- Gabriela Serrão Abreu Conceição
- Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Karem Paula Pinto
- Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Claudio Malizia Alves Ferreira
- Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Jenif Braga de Souza
- Laboratory of Experimental Surgery, School of Medical Sciences, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Ricardo Tadeu Lopes
- Nuclear Engineering Program, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Bárbara P Coelho
- Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Luciana Moura Sassone
- Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Emmanuel João Nogueira Leal da Silva
- Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
- Departament of Endodontics, Grande Rio University (UNIGRANRIO), Rio de Janeiro, Brazil
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Ling Q, Wang AJ, Wang XY. Chemokine receptor-2 deficiency induced mild experimental periapical lesion in mice. J Dent Sci 2025; 20:402-409. [PMID: 39873018 PMCID: PMC11762637 DOI: 10.1016/j.jds.2024.06.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 06/04/2024] [Indexed: 01/30/2025] Open
Abstract
Background/purpose Macrophages are considered to play an important role in the development of chronic apical periodontitis (CAP). However the function of tissue resident macrophages in CAP is unclear. This study aims to investigate the potential role of macrophages of different origins in CAP. Materials and methods Chemokine receptor-2 deficiency (CCR2-/-) mice and C57BL/6N mice (control group, WT mice) were used to induce apical periodontitis. The pulp of mandibular first molars of both sides were exposed to the oral environment. After 0, 7, 21, 28 days of pulp explosion, animals were sacrificed, the mandibular bones were collected and scanned with micro-CT, further processed for HE & IHC Staining to analyze the development of CAP, as well as the expression of surface markers of macrophages. Results Both CCR2-/- and WT mice exhibited CCR2 negative macrophages in normal periapical area, which indicated the presence of tissue resident macrophages. CCR2 deficiency decreased the number of macrophages in periapical lesions, the M1 type macrophages' number as well as osteoclasts around the edge of the lesion decreased compared to wild type. Meanwhile CCR2 deficiency decreased the volume of periapical lesion significantly compared to wild type, but did not inhibite and disappeare the lesion thoroughly. Conclusion Monocyte-macrophage system derived macrophages promote the progression of periapical lesions, while tissue resident macrophages in periodontal ligament might also be involved in the progression of periapical lesion.
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Affiliation(s)
- Qiao Ling
- Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology, Beijing, China
- National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing, China
| | - Ai-jing Wang
- Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology, Beijing, China
- National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing, China
| | - Xiao-yan Wang
- Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology, Beijing, China
- National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing, China
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Wang X, Chen X, Gao J, Jin Z. Transient Receptor Potential Ankyrin 1 (TRPA1) Mediated LPS-Induced Inflammation in Periodontal Ligament Stem Cells by Inhibiting the Phosphorylation of JNK. Stem Cells Int 2024; 2024:7461604. [PMID: 39735214 PMCID: PMC11679270 DOI: 10.1155/sci/7461604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Accepted: 11/07/2024] [Indexed: 12/31/2024] Open
Abstract
Transient receptor potential ankyrin 1 (TRPA1) molecule is an important type of transient receptor potential (TRP) cation channels, which can cause extracellular Ca2+ to flow into cells after activation. TRPA1 plays an important role in acute and chronic pain, inflammation, kidney disease, cough and asthma, osteoarthritis, cardiovascular disease, obesity, diabetes, and other diseases. In this study, the expression of interleukin (IL)-1β, IL-6, and IL-8 in periodontal ligament stem cells (PDLSCs) treated by lipopolysaccharide (LPS) and the effect of LPS on PDLSCS proliferation were detected. Meanwhile, the change in TRPA1 expression in PDLSCs treated by LPS was also assessed. By knocking down the expression of TRPA1 and using the TRPA1 antagonist HC-030031, the expression of IL-1β, IL-6, and IL-8 in PDLSCs treated by LPS was downregulated. After LPS stimulation, the proliferation ability of PDLSCs decreased, the gene expression and secretion of IL-1β, IL-6, and IL-8 increased and the gene and protein expression of TRPA1 were upregulated. Reducing the expression of TRPA1 can effectively inhibit the increase of gene expression of IL-1β, IL-6, and IL-8 after LPS stimulation, and pretreatment of PDLSCs with HC-030031 can also achieve the above effect. And research has found that HC-030031 can inhibit the phosphorylation level of JNK in PDLSCs treated by LPS. The use of JNK inhibitor JNK-IN-8 can also reduce the expression of IL-1β, IL-6, and IL-8 in PDLSCs. Finally, this study found LPS could cause the upregulation of TRPA1, and the inhibition of TRPA1 could produce an anti-inflammatory effect in PDLSCs treated by LPS due to its inhibition of JNK phosphorylation.
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Affiliation(s)
- Xian Wang
- State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, No. 169 Changle West Road, Xi'an 710032, China
| | - Xin Chen
- State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, No. 169 Changle West Road, Xi'an 710032, China
| | - Jie Gao
- State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, No. 169 Changle West Road, Xi'an 710032, China
| | - Zuolin Jin
- State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, No. 169 Changle West Road, Xi'an 710032, China
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Uygun AD, Şen S, Çelik S. Comparison of biocompatibility of epoxy resin and bioceramic-based root canal sealers. Clin Oral Investig 2024; 28:673. [PMID: 39617835 DOI: 10.1007/s00784-024-06071-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 11/23/2024] [Indexed: 12/20/2024]
Abstract
OBJECTIVES The purpose of this study is to compare the cytotoxicity of 2 bioceramic-based (Bioserra and AH Plus Bioceramic (Bio)) and 2 epoxy resin-based (Sealart and AH Plus) root canal sealers on the Saos-2 cell line. METHODS The cytotoxicity of the root canal sealers was determined using the MTT metabolic activity assay. The mRNA expression levels of Bcl-2, Beclin1, Cas-3, IL-6, LC3, MMP-9 and TNF-α genes were assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and the expression of Beclin1 and LC3 proteins were assessed using western blot (WB) method. The canal sealers' total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were measured using photometric kits. RESULTS AH Plus Bio significantly increased metabolic activity compared to the 2 resin-containing sealers, but there was no difference with Bioserra. Sealart was clearly the most cytotoxic group. QRT-PCR analysis revealed that the mRNA expressions of Bcl-2, Beclin1, Cas-3, IL-6, LC3, and MMP-9 in the Bioserra group, Bcl-2, Cas-3, and IL-6 in the Sealart group, Beclin1, Cas-3, IL-6, and MMP-9 in the AH Plus group, and Bcl2 in the AH Plus Bio group were stimulated. The OSI results showed no significant difference between the root canal sealer groups. CONCLUSIONS In the study, the best biocompatibility results in MTT, qRT-PCR, WB and OSI were in the AH Plus Bio group. Although Bioserra, the study's other bioceramic paste, was found to be biocompatible according to MTT and OSI measurements, it increased the expression of all genes in qRT-PCR except for TNF-α, and also increased LC3 protein levels in WB. CLINICAL RELEVANCE Since periradicular tissues can be directly affected by the materials used in root canal treatment, the sealers with high biocompatibility are being developed. In vitro studies examining the biocompatibility of newly produced root canal sealers are guiding for clinical success.
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Affiliation(s)
- Ahmet Demirhan Uygun
- Department of Endodontics, Faculty of Dentistry, Afyonkarahisar Health Sciences University, Afyonkarahisar, 03030, Turkey.
| | - Serkan Şen
- Department of Medical Laboratory Techniques, Atatürk Vocational School of Health Services, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey
| | - Sefa Çelik
- Department of Medical Biochemistry, Faculty of Medicine, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey
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Matos-Sousa JM, Souza-Monteiro D, dos Santos VRN, Ferreira MKM, Frazão DR, Chemelo VS, Bittencourt LDO, Moura JDMD, Maia CDSF, Collares FM, Fernandes LDMP, Lima RR. High-intensity ethanol binge drinking accentuates bone damage in induced apical periodontitis in rats. Heliyon 2024; 10:e40163. [PMID: 39641066 PMCID: PMC11617731 DOI: 10.1016/j.heliyon.2024.e40163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Revised: 10/28/2024] [Accepted: 11/05/2024] [Indexed: 12/07/2024] Open
Abstract
This study aimed to evaluate the effects of excessive and episodic consumption of ethanol (EtOH, a high-intensity drinking manner) on induced apical periodontitis in rats. Thirty-two animals were divided into the following four groups: control, EtOH, apical periodontitis, and EtOH + apical periodontitis. Ethanol exposure (3 g/kg 20 % w/v EtOH) was performed by orogastric gavage for 3 consecutive days, followed by 4 days of withdrawal for 4 weeks. Lesions were induced by exposing the dental pulp of the lower first molar and by the absence of any treatment/curative for 28 days. Finally, the animals were euthanized, and mandibles were collected. The mandible was divided medially, with one hemimandible being used for micro-computed tomography analysis of the volume of the periapical lesion and bone quality parameters, such as bone volume and trabecular bone assessments; the other hemimandible was used for histological analysis, with a descriptive histopathological analysis of the tissue and the pattern of bone loss presented, as well as an assessment of the collagen content present. The data were subjected to statistical analysis (one-way analysis of variance with Tukey's post-hoc test). Our results showed that the EtOH + apical periodontitis group had a larger volume of periapical lesions than animals that were not exposed to ethanol. Additionally, bone quality parameters showed a reduction in bone volume and thickening of the trabeculae, associated with increased tissue destruction and reduced collagen content in the remnant region of the alveolar bone. These results suggest that exposure to EtOH in a pattern of excessive alcohol consumption is an aggravating factor in apical periodontitis and, consequently, in its progression, the quality and quantity of the alveolar bone remaining in the region of the periapical lesion are the modulating aspects.
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Affiliation(s)
- José Mário Matos-Sousa
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil
| | - Deiweson Souza-Monteiro
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil
| | - Vinicius Ruan Neves dos Santos
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil
| | - Maria Karolina Martins Ferreira
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil
| | - Deborah Ribeiro Frazão
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil
| | - Victória Santos Chemelo
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil
| | - Leonardo de Oliveira Bittencourt
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil
| | - João Daniel Mendonça de Moura
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil
| | - Cristiane do Socorro Ferraz Maia
- Laboratory of Inflammation and Behavioral Pharmacology, Institute of Health Sciences, Federal University of Pará, Belém, Pará, Brazil
| | - Fabrício Mezzomo Collares
- Laboratory of Dental Materials, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Luanna de Melo Pereira Fernandes
- Laboratory of Neuropharmacology and Behavior, Center for Biological |Health Sciences, State University of Pará, Belém, Pará, Brazil
| | - Rafael Rodrigues Lima
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil
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Dobrzyńska-Mizera M, Knitter M, Kamińska M, Szymanowska D, Sobczyk-Guzenda A, Różańska S, Różański J, Mikulski M, Muzalewska M, Wyleżoł M, Smuga-Kogut M, Modrzejewska Z, Di Lorenzo ML. Thermosensitive hydrogel doped with osteoconductive fillers for the treatment of periodontitis periapicalis chronica: from synthesis to clinical trial. Biomater Sci 2024; 12:6063-6081. [PMID: 39422703 DOI: 10.1039/d4bm00927d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2024]
Abstract
Herein, a chitosan-based thermosensitive hydrogel (CH) containing hydroxyapatite (HAp), poly(lactic acid) (PLDLLA) or their mixture is proposed as an innovative, biomimetic composition with antimicrobial and bone-forming properties for guided bone regeneration. The modified hydrogels were synthesized and characterized to verify their suitability for the treatment of periodontitis periapicalis chronica. Compared to the unmodified hydrogel, both CH_HAp and CH_PLDLLA revealed improved mechanical properties, as evidenced by rotational rheology. FTIR analysis proved that no chemical interplay existed between the components. All the tested samples displayed no cytotoxicity against osteoblast-like cell culture and confirmed antimicrobial features, both crucial from an application perspective. Radiation sterilization dosage was tailored for the tested samples to maintain sterility for a minimum of 8 weeks of storage and limit crosslinking of the samples. Finally, the hydrogel was used in a clinical trial to treat a patient with chronic inflammation of periapical tissues in teeth 26 and 27. The medical procedure proved the safety, nontoxicity, non-allergenicity, and, most importantly, bone-forming properties of the hydrogel formulation. The kinetics of new bone formation was analyzed in-depth using graphical cross-sections of anatomical structures obtained from pre- and post-operative CBCT scans.
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Affiliation(s)
- Monika Dobrzyńska-Mizera
- Institute of Materials Technology, Polymer Division, Poznan University of Technology, Piotrowo 3, 61-138 Poznan, Poland.
| | - Monika Knitter
- Institute of Materials Technology, Polymer Division, Poznan University of Technology, Piotrowo 3, 61-138 Poznan, Poland.
| | - Marta Kamińska
- Institute of Materials Science and Engineering, Faculty of Mechanical Engineering, Lodz University of Technology, Stefanowskiego 1/15, 90-537 Lodz, Poland
| | - Daria Szymanowska
- Department of Pharmacognosy and Biomaterials, Faculty of Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland
- Department of Biotechnology and Food Microbiology, Poznan University of Life Sciences, Wojska Polskiego 48, 60-627 Poznan, Poland
| | - Anna Sobczyk-Guzenda
- Institute of Materials Science and Engineering, Faculty of Mechanical Engineering, Lodz University of Technology, Stefanowskiego 1/15, 90-537 Lodz, Poland
| | - Sylwia Różańska
- Institute of Chemical Technology and Engineering, Division of Chemical Engineering and Equipment, Poznan University of Technology, Berdychowo 4, 60-965 Poznan, Poland
| | - Jacek Różański
- Institute of Chemical Technology and Engineering, Division of Chemical Engineering and Equipment, Poznan University of Technology, Berdychowo 4, 60-965 Poznan, Poland
| | - Michał Mikulski
- Artdent Dental Office, Piekarska 11-13, 62-800 Kalisz, Poland
| | - Małgorzata Muzalewska
- Department of Fundamentals of Machinery Design, Faculty of Mechanical Engineering, Silesian University of Technology, Konarskiego 18A, 44-100 Gliwice, Poland
| | - Marek Wyleżoł
- Department of Fundamentals of Machinery Design, Faculty of Mechanical Engineering, Silesian University of Technology, Konarskiego 18A, 44-100 Gliwice, Poland
| | - Małgorzata Smuga-Kogut
- Department of Agrobiotechnology, Faculty of Mechanical Engineering, Koszalin University of Technology, Raclawicka 15-17, 75-620 Koszalin, Poland
| | - Zofia Modrzejewska
- Faculty of Process and Environmental Engineering, Lodz University of Technology, 93-005 Lodz, Poland
| | - Maria Laura Di Lorenzo
- National Research Council (CNR), Institute of Polymers, Composites and Biomaterials (IPCB), Via Campi Flegrei, 34, 80078 Pozzuoli, NA, Italy
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Chen Y, Ullah A, Chen W, Xuan J, Huang X, Liang S, Shen B, Wu T. Cytokine modulation in pelvic organ prolapse and urinary incontinence: from molecular insights to therapeutic targets. Mol Med 2024; 30:214. [PMID: 39538179 PMCID: PMC11562709 DOI: 10.1186/s10020-024-00989-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Accepted: 11/05/2024] [Indexed: 11/16/2024] Open
Abstract
Pelvic organ prolapse (POP) and urinary incontinence (UI) are common disorders that significantly impact women's quality of life. Studies have demonstrated that cytokines, including pro- and anti-inflammatory immune mediators, play a role in illness genesis and progression. Research on the inflammatory milieu of the pelvic floor has shown that POP patients have increased inflammation in vaginal tissues. This evidence revealed that significant changes in the inflammatory milieu of the pelvic floor are an aspect of the pathogenesis of POP. POP patients exhibit increased levels of inflammatory cytokines (IL-1, TNF, IFN, and others) in the front vaginal wall, which may alter collagen metabolism and contribute to POP. Studies indicate that cytokines such as IL-6, IL-10, and TGF, which are involved in inflammation, remodelling, and repair, have dual effects on POP and UI. They can promote tissue healing and regeneration but also exacerbate inflammation and fibrosis, contributing to the progression of these conditions. Understanding the dual roles of these cytokines could help us improve the vaginal microenvironment of women and treat POP and UI. Given the considerable changes in these cytokines, this review addresses studies published between 2000 and 2024 on the molecular mechanisms by which pro- and anti-inflammatory cytokines affect women with POP and UI. Furthermore, we explain novel therapeutic strategies for cytokine regulation, emphasizing the possibility of personalized treatments that address the underlying inflammatory milieu of the vagina in POP and UI patients. This thorough analysis aims to establish a foundation for future research and clinical applications, ultimately improving patient outcomes via designed cytokine-based therapies.
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Affiliation(s)
- Yongxiu Chen
- Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, China
- Gynecology Department, Guangdong Women and Children Hospital, Guangzhou, China
| | - Amin Ullah
- Department of Abdominal Oncology, Cancer Center of West China Hospital and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Weifang Chen
- Gynecology Department, Guangdong Women and Children Hospital, Guangzhou, China
| | - Jianyan Xuan
- Gynecology Department, Guangdong Women and Children Hospital, Guangzhou, China
| | - Xiaowen Huang
- Gynecology Department, Guangdong Women and Children Hospital, Guangzhou, China
| | - Shiqi Liang
- Gynecology Department, Guangdong Women and Children Hospital, Guangzhou, China
| | - Bairong Shen
- Department of Abdominal Oncology, Cancer Center of West China Hospital and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
| | - Tingfeng Wu
- Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.
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Wen YH, Lin YX, Zhou L, Lin C, Zhang L. The immune landscape in apical periodontitis: From mechanism to therapy. Int Endod J 2024; 57:1526-1545. [PMID: 39087849 DOI: 10.1111/iej.14125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 07/04/2024] [Accepted: 07/12/2024] [Indexed: 08/02/2024]
Abstract
Apical periodontitis (AP) is featured by a persistent inflammatory response and alveolar bone resorption initiated by microorganisms, posing risks to both dental and systemic health. Nonsurgical endodontic treatment is the recommended treatment plan for AP with a high success rate, but in some cases, periapical lesions may persist despite standard endodontic treatment. Better comprehension of the AP inflammatory microenvironment can help develop adjunct therapies to improve the outcome of endodontic treatment. This review presents an overview of the immune landscape in AP, elucidating how microbial invasion triggers host immune activation and shapes the inflammatory microenvironment, ultimately impacting bone homeostasis. The destructive effect of excessive immune activation on periapical tissues is emphasized. This review aimed to systematically discuss the immunological basis of AP, the inflammatory bone resorption and the immune cell network in AP, thereby providing insights into potential immunotherapeutic strategies such as targeted therapy, antioxidant therapy, adoptive cell therapy and cytokine therapy to mitigate AP-associated tissue destruction.
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Affiliation(s)
- Yuan-Hao Wen
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Yu-Xiu Lin
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
- Department of Cariology and Endodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Lu Zhou
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
- Department of Cariology and Endodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Chen Lin
- Department of Endodontics, Stomatological Hospital of Xiamen Medical College, Xiamen, China
| | - Lu Zhang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
- Department of Cariology and Endodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, China
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10
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Sun J, Feng S, Ding T, Wang T, Du L, Kang W, Ge S. Fusobacterium nucleatum dysregulates inflammatory cytokines and NLRP3 inflammasomes in oral cells. Oral Dis 2024; 30:4767-4781. [PMID: 38409736 DOI: 10.1111/odi.14899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 01/14/2024] [Accepted: 02/06/2024] [Indexed: 02/28/2024]
Abstract
OBJECTIVE This study aimed to clarify the difference in Fusobacterium nucleatum (F. nucleatum) induced inflammatory cytokines and nod-like receptor protein 3 (NLRP3) inflammasomes dysregulation among three periodontal cells. METHODS Oral epithelial cells (HIOECs), THP-1 macrophages, and human gingival fibroblasts (HGFs) were exposed to F. nucleatum with/without adenosine triphosphate (ATP) and nigericin (Nig). Cell morphology was assessed by scanning electron microscopy. qRT-PCR, protein microarrays, and bioinformatic methods were used to evaluate the cytokines and their complex interplay. NLRP3 inflammasomes activation was detected by western blotting and ELISA. RESULTS F. nucleatum adhered to and invaded cells. In HIOECs, F. nucleatum enhanced interleukin (IL)-1α/1β/6/10/13, TNF-α, and interferon (IFN)-γ expression. In THP-1 macrophages, F. nucleatum up-regulated IL-1α/1β/6/10 and TNF-α levels. In HGFs, F. nucleatum increased IL-6 levels. F. nucleatum and ATP synergistically boosted IFN-γ level in THP-1 macrophages and IL-13 level in HGFs. IL-1α/1β/6, and TNF-α served as epicenters of the inflammatory response. Additionally, F. nucleatum activated NLRP3 inflammasomes in HIOECs, and ATP/Nig boosted the activation. F. nucleatum also triggered NLRP3 inflammasomes in THP-1 macrophages, but in HGFs, only NLRP3 and caspase-1 levels were elevated. CONCLUSION F. nucleatum infiltrated periodontal supporting cells and dysregulated inflammatory cytokines and NLRP3 inflammasomes.
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Affiliation(s)
- Jingzhuo Sun
- Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China
| | - Susu Feng
- Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China
| | - Tian Ding
- Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China
| | - Ting Wang
- Department of General Dentistry, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China
| | - Lingqian Du
- Department of Stomatology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Wenyan Kang
- Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China
| | - Shaohua Ge
- Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China
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11
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Duarte Faria F, Cantiga-Silva C, Cardoso CDBM, da Silva Machado NE, de Oliveira PHC, Justo MP, Goto J, de Castilho Jacinto R, Sivieri-Araújo G, Cintra LTA. Influence of systemic antibiotic therapy on the development and progression of induced apical periodontitis in Wistar rats. Odontology 2024; 112:1080-1089. [PMID: 38457086 DOI: 10.1007/s10266-024-00908-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Accepted: 01/29/2024] [Indexed: 03/09/2024]
Abstract
The aim of this study was to investigate the influence of systemic antibiotic therapy on the development and progression of induced apical periodontitis (AP) in Wistar rats. Fifty-six rats were submitted to pulp exposure of the lower left first molar for the induction of AP. On the same day, intraperitoneal antibiotic therapy was administered once a day, for 15 days, until euthanasia. The groups were formed according to the different treatments (n = 8): C-control; GEN-treated with gentamicin (10 mg/Kg); AC-treated with amoxicillin (100 mg/Kg); MZ-treated with metronidazole (40 mg/Kg); AMP-treated with ampicillin (100 mg/Kg); AMC group-treated with amoxicillin + clavulanic acid (100 mg/kg); CLI-treated with clindamycin (60 mg/kg). After euthanasia, the jaws were collected and processed for (1) histological and histometric analysis using hematoxylin and eosin staining, (2) analysis of collagen fibers using Picrosirius Red staining and (3) bacteriological analysis using Brown-Brenn staining. The data were analyzed statistically (p < 0.05). AP induction was confirmed in all groups. The AMC group had the lower intensity of inflammatory infiltrate (p = 0.028) and less periapical bone resorption compared to control (p = 0.006). Regarding collagen maturation, PSR staining revealed a predominance of mature collagen fibers in all groups. The AC and AMC groups had the lower amount of mature fibers and the highest amount of immature fibers, compared to all other groups (p < 0.001). All groups showed bacterial contamination; however, the AC and AMC groups showed a lower extent of bacterial contamination compared to the control (p < 0.001). It can be concluded that systemic antibiotic therapy influences the development and progression of induced AP.
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Affiliation(s)
- Flávio Duarte Faria
- Department of Preventive and Restorative Dentistry, School of Dentistry, São Paulo State University (Unesp), José Bonifácio, 1193, Vila Mendonça, Araçatuba, SP, 16015-050, Brazil
| | - Cristiane Cantiga-Silva
- Department of Preventive and Restorative Dentistry, School of Dentistry, São Paulo State University (Unesp), José Bonifácio, 1193, Vila Mendonça, Araçatuba, SP, 16015-050, Brazil
| | - Carolina de Barros Morais Cardoso
- Department of Preventive and Restorative Dentistry, School of Dentistry, São Paulo State University (Unesp), José Bonifácio, 1193, Vila Mendonça, Araçatuba, SP, 16015-050, Brazil
| | - Nathália Evelyn da Silva Machado
- Department of Preventive and Restorative Dentistry, School of Dentistry, São Paulo State University (Unesp), José Bonifácio, 1193, Vila Mendonça, Araçatuba, SP, 16015-050, Brazil
| | - Pedro Henrique Chaves de Oliveira
- Department of Preventive and Restorative Dentistry, School of Dentistry, São Paulo State University (Unesp), José Bonifácio, 1193, Vila Mendonça, Araçatuba, SP, 16015-050, Brazil
| | - Mariana Pagliusi Justo
- Department of Preventive and Restorative Dentistry, School of Dentistry, São Paulo State University (Unesp), José Bonifácio, 1193, Vila Mendonça, Araçatuba, SP, 16015-050, Brazil
| | - Juliana Goto
- Department of Preventive and Restorative Dentistry, School of Dentistry, São Paulo State University (Unesp), José Bonifácio, 1193, Vila Mendonça, Araçatuba, SP, 16015-050, Brazil
| | - Rogério de Castilho Jacinto
- Department of Preventive and Restorative Dentistry, School of Dentistry, São Paulo State University (Unesp), José Bonifácio, 1193, Vila Mendonça, Araçatuba, SP, 16015-050, Brazil
| | - Gustavo Sivieri-Araújo
- Department of Preventive and Restorative Dentistry, School of Dentistry, São Paulo State University (Unesp), José Bonifácio, 1193, Vila Mendonça, Araçatuba, SP, 16015-050, Brazil
| | - Luciano Tavares Angelo Cintra
- Department of Preventive and Restorative Dentistry, School of Dentistry, São Paulo State University (Unesp), José Bonifácio, 1193, Vila Mendonça, Araçatuba, SP, 16015-050, Brazil.
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12
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Wu H, Wang L, Qiu C. Causal relationship, shared genes between rheumatoid arthritis and pulp and periapical disease: evidence from GWAS and transcriptome data. Front Immunol 2024; 15:1440753. [PMID: 39346909 PMCID: PMC11427265 DOI: 10.3389/fimmu.2024.1440753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 08/27/2024] [Indexed: 10/01/2024] Open
Abstract
Objective Patients with rheumatoid arthritis (RA) have an increased risk of developing pulp and periapical disease (PAP), but the causal relationship and shared genetic factors between these conditions have not been explored. This study aimed to investigate the bidirectional causal relationship between RA and PAP and to analyze shared genes and pathogenic pathways. Methods We utilized GWAS data from the IEU Open GWAS Project and employed five Mendelian randomization methods (MR Egger, weighted median, inverse variance weighted, simple mode, and weighted mode) to investigate the bidirectional causal relationship between RA and PAP. Transcriptome data for RA and irreversible pulpitis (IRP) were obtained from the GEO database. Hub genes were identified through differential analysis, CytoHubba, machine learning (ML), and other methods. The immune infiltration of both diseases was analyzed using the ssGSEA method. Finally, we constructed a regulatory network for miRNAs, transcription factors, chemicals, diseases, and RNA-binding proteins based on the identified hub genes. Results RA was significantly associated with an increased risk of PAP (OR = 1.1284, 95% CI 1.0674-1.1929, p < 0.001). However, there was insufficient evidence to support the hypothesis that PAP increased the risk of RA. Integrating datasets and differential analysis identified 84 shared genes primarily involved in immune and inflammatory pathways, including the IL-17 signaling pathway, Th17 cell differentiation, and TNF signaling pathway. Using CytoHubba and three ML methods, we identified three hub genes (HLA-DRA, ITGAX, and PTPRC) that are significantly correlated and valuable for diagnosing RA and IRP. We then constructed a comprehensive regulatory network using the miRDB, miRWalk, ChipBase, hTFtarget, CTD, MalaCards, DisGeNET, and ENCORI databases. Conclusion RA may increase the risk of PAP. The three key genes, HLA-DRA, ITGAX, and PTPRC, have significant diagnostic value for both RA and IRP.
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Affiliation(s)
- Huili Wu
- Department of Endodontics, Changzhou Stomatological Hospital,
Changzhou, China
| | - Lijuan Wang
- Department of Endodontics, Changzhou Stomatological Hospital,
Changzhou, China
| | - Chenjie Qiu
- Department of General Surgery, Changzhou Hospital of Traditional Chinese
Medicine, Changzhou, China
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13
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Mota ME, Franco JB, Alves FA, Moreira MS. Precision dentistry in patients undergoing hematopoietic stem cell transplantation. Oral Dis 2024; 30:4056-4058. [PMID: 38217442 DOI: 10.1111/odi.14866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Revised: 11/20/2023] [Accepted: 12/29/2023] [Indexed: 01/15/2024]
Affiliation(s)
- Maria Emília Mota
- Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, Brazil
| | - Juliana Bertoldi Franco
- Division of Dentistry of the Clinics Hospital of the University of São Paulo School of Medicine, São Paulo, Brazil
| | - Fábio Abreu Alves
- Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, Brazil
- Department of Stomatology, A.C. Camargo Cancer Center, São Paulo, Brazil
| | - Maria Stella Moreira
- Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, Brazil
- Department of Stomatology, A.C. Camargo Cancer Center, São Paulo, Brazil
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Abdulhadi ZT, Mahdee AF, Gul SS. Accuracy of Gingival Crevicular Fluid Biomarkers of MMP8, TIMP1, RANK, RANKL, and OPG in Differentiating Symptomatic and Asymptomatic Apical Periodontitis. Diagnostics (Basel) 2024; 14:1872. [PMID: 39272657 PMCID: PMC11394092 DOI: 10.3390/diagnostics14171872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 08/14/2024] [Accepted: 08/22/2024] [Indexed: 09/15/2024] Open
Abstract
Apical periodontitis (AP) is the most prevalent chronic inflammatory disease of the teeth. Bone resorption dynamics in symptomatic and asymptomatic AP are still unrecognized. This study examined different inflammatory markers within gingival crevicular fluid, including matrix metalloproteinases 8 (MMP8), tissue inhibitors of metalloproteinases 1 (TIMP1), receptor activator of nuclear factor κB (RANK), its ligand (RANKL), and osteoprotegerin (OPG), to be used in comparing symptomatic apical periodontitis (SAP) and asymptomatic apical periodontitis (AAP) versus healthy teeth. Subjects with SAP, AAP, and a control group were recruited and GCF samples were collected by Periopaper strips. Clinical and radiographical measures were used for diagnosing AP. Levels of MMP8, TIMP, RANK, RANKL, and OPG were determined by ELISA and their abilities to discriminate between examined sites were evaluated by receiver operator characteristic (ROC) curves. All examined biomarkers were statistically significant higher (p < 0.05) in SAP than AAP and the control group, apart from RANK. Significant positive correlations (p < 0.05) were identified between all SAP and AAP biomarkers except TIMP1 and RANK in AAP teeth. TIMP1 and OPG exhibited the highest ability to distinguish between SAP and AAP with areas under the curve of 0.824 and 0.763 in comparing SAP and the control group, and 0.732 and 0.73 when comparing AAP and the control group, respectively. Additionally, TIMP1 and OPG showed the highest AUC of 0.778 and 0.747 when SAP and AAP were compared, respectively. This study concluded that GCF levels of TIMP1 and OPG can be used to differentiate between SAP, AAP, and healthy teeth.
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Affiliation(s)
- Zeena Tariq Abdulhadi
- Department of Restorative and Aesthetic Dentistry, College of Dentistry, University of Baghdad, Baghdad 10071, Iraq
| | - Anas Falah Mahdee
- Department of Restorative and Aesthetic Dentistry, College of Dentistry, University of Baghdad, Baghdad 10071, Iraq
| | - Sarhang Sarwat Gul
- Medical Laboratory Department, College of Health and Medical Technology, Sulaimani Polytechnic University, Sulaymaniyah 46001, Iraq
- Department of Periodontics, College of Dentistry, University of Sulaimani, Sulaymaniyah 46001, Iraq
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15
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Neurath N, Kesting M. Cytokines in gingivitis and periodontitis: from pathogenesis to therapeutic targets. Front Immunol 2024; 15:1435054. [PMID: 39253090 PMCID: PMC11381234 DOI: 10.3389/fimmu.2024.1435054] [Citation(s) in RCA: 19] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Accepted: 08/02/2024] [Indexed: 09/11/2024] Open
Abstract
Chronic inflammatory processes in the oral mucosa and periodontitis are common disorders caused by microflora and microbial biofilms. These factors activate both the innate and adaptive immune systems, leading to the production of pro-inflammatory cytokines. Cytokines are known to play a crucial role in the pathogenesis of gingivitis and periodontitis and have been proposed as biomarkers for diagnosis and follow-up of these diseases. They can activate immune and stromal cells, leading to local inflammation and tissue damage. This damage can include destruction of the periodontal ligaments, gingiva, and alveolar bone. Studies have reported increased local levels of pro-inflammatory cytokines, such as interleukin-1beta (IL-1beta), tumor necrosis factor (TNF), IL-6, IL-17, and IL-23, in patients with periodontitis. In experimental models of periodontitis, TNF and the IL-23/IL-17 axis play a pivotal role in disease pathogenesis. Inactivation of these pro-inflammatory pathways through neutralizing antibodies, genetic engineering or IL-10 function has been demonstrated to reduce disease activity. This review discusses the role of cytokines in gingivitis and periodontitis, with particular emphasis on their role in mediating inflammation and tissue destruction. It also explores new therapeutic interventions that offer potential for research and clinical therapy in these chronic inflammatory diseases.
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Affiliation(s)
- Nicole Neurath
- Department of Oral and Cranio-Maxillofacial Surgery, Uniklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
- Deutsches Zentrum Immuntherapie DZI, Uniklinikum Erlangen, Erlangen, Germany
| | - Marco Kesting
- Department of Oral and Cranio-Maxillofacial Surgery, Uniklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
- Deutsches Zentrum Immuntherapie DZI, Uniklinikum Erlangen, Erlangen, Germany
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16
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Wang K, Liu J, Yue J, Zhou L, Mao H, Li J, Sun Z, Chen Z, Zhang L. Nlrp3 inflammasome drives regulatory T cell depletion to accelerate periapical bone erosion. Int Endod J 2024; 57:1110-1123. [PMID: 38441141 DOI: 10.1111/iej.14062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 02/24/2024] [Accepted: 02/26/2024] [Indexed: 07/03/2024]
Abstract
AIM Apical periodontitis is an inflammatory disorder triggered by an immune response to bacterial infection, leading to the periapical tissue damage and alveolar resorption. However, the underlying mechanisms driving this process remain elusive, due to the complex and interconnected immune microenvironment within the local lesion site. In this study, the influence of Nlrp3 inflammasome-mediated immune response on the apical periodontitis was investigated. METHODOLOGY RNA sequencing, immunohistochemistry and ELISA assay were performed to investigate the activation of Nlrp3 inflammasome signalling pathways in the human periapical tissues, including radicular cysts, periapical granulomas and healthy oral mucosa. A mouse model of apical periodontitis was established to study the role of Nlrp3 knockout in periapical bone resorption and Treg cell stability, and the underlying mechanism was explored through in vitro experiments. In vivo Treg cell adoptive transfer was performed to investigate the effects of Treg cells on the progression of apical periodontitis. RESULTS Our findings find that the hyperactivated Nlrp3 inflammasome is present in human periapical lesions and plays a vital role in the immune-related periapical bone loss. Using a mouse model of apical periodontitis, we observe that Nlrp3 deficiency is resistant to bone resorption. This protection was accompanied by elevated generation and infiltration of local Treg cells that displayed a notable ability to suppress RANKL-dependent osteoclast differentiation. In terms of the mechanism of action, Nlrp3 deficiency directly inhibits the osteoclast differentiation and bone loss through JNK/MAPK and NF-κB pathways. In addition, Nlrp3 induces pyroptosis in the stem cells from apical papilla (SCAPs), and the subsequent release of cytokines affects the stability of Treg cell in periapical lesions, leading indirectly to enhanced bone resorption. In turn, adoptive transfer of both Nlrp3-deficient and wild-type Treg cells effectively prevent the bone erosion during apical periodontitis. CONCLUSIONS Together, our data identify that the Nlrp3 inflammasome modulates the Treg cell stability and osteoclastogenesis in the periapical inflammatory microenvironment, thus determining the progression of bone erosion.
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Affiliation(s)
- Konghuai Wang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Jiayi Liu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Junli Yue
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
- Department of Endodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Lu Zhou
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Hanqing Mao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Jiaqi Li
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Zhijun Sun
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
- Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Zhi Chen
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
- Department of Endodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Lu Zhang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
- Department of Endodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, China
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Relvas M, Mendes-Frias A, Gonçalves M, Salazar F, López-Jarana P, Silvestre R, Viana da Costa A. Salivary IL-1β, IL-6, and IL-10 Are Key Biomarkers of Periodontitis Severity. Int J Mol Sci 2024; 25:8401. [PMID: 39125970 PMCID: PMC11312971 DOI: 10.3390/ijms25158401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Revised: 07/11/2024] [Accepted: 07/26/2024] [Indexed: 08/12/2024] Open
Abstract
To explore severity and progression biomarkers, we examined the clinical relevance of multiple cytokines and mediators involved in the inflammatory response in periodontitis. A cohort of 68 patients was enrolled in the study and periodontal status assessed by the current classification of periodontal diseases. Immune mediators present in saliva, of both patients and healthy controls, were quantified using a Legendplex-13 panel. Clinic parameters were significantly higher in PD patients compared with HC, with a strong significant association with the disease severity (stage) (p < 0.001), but not with progression (grade). The panel of immune mediators evidenced elevated levels of pro-inflammatory cytokines IL-6 and IL-1β as disease established (p < 0.01). IL-1β/IL-1RA ratio was increased in PD patients, being associated with disease stage. An anti-inflammatory response was spotted by higher IL-10. Lower levels of IL-23 and IP-10 were associated with disease severity. No significant statistical differences were found by grade classification. Moreover, salivary IL-1β and IL-6 exhibited significant positive correlations with several clinical measurements (PI, BOP, PPD, CAL), while IP-10 showed a statistical negative correlation with BOP, PPD, and CAL. These insights highlight the complexity of the periodontitis inflammatory network and the potential of cytokines as biomarkers for refined diagnostic and therapeutic strategies.
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Affiliation(s)
- Marta Relvas
- University Institute of Health Sciences (IUCS-CESPU), 4585-116 Gandra, Portugal; (M.G.); (F.S.); (P.L.-J.); (A.V.d.C.)
- Oral Pathology and Rehabilitation Research Unit (UNIPRO), University Institute of Health Sciences (IUCS-CESPU), CRL, 4585-116 Gandra, Portugal
| | - Ana Mendes-Frias
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal; (A.M.-F.); (R.S.)
- ICVS/3B’s—PT Government Associate Laboratory, 4710-057 Braga, Portugal
| | - Maria Gonçalves
- University Institute of Health Sciences (IUCS-CESPU), 4585-116 Gandra, Portugal; (M.G.); (F.S.); (P.L.-J.); (A.V.d.C.)
- UCIBIO—Applied Molecular Biosciences Unit, Toxicologic Pathology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal
| | - Filomena Salazar
- University Institute of Health Sciences (IUCS-CESPU), 4585-116 Gandra, Portugal; (M.G.); (F.S.); (P.L.-J.); (A.V.d.C.)
- Oral Pathology and Rehabilitation Research Unit (UNIPRO), University Institute of Health Sciences (IUCS-CESPU), CRL, 4585-116 Gandra, Portugal
| | - Paula López-Jarana
- University Institute of Health Sciences (IUCS-CESPU), 4585-116 Gandra, Portugal; (M.G.); (F.S.); (P.L.-J.); (A.V.d.C.)
- Oral Pathology and Rehabilitation Research Unit (UNIPRO), University Institute of Health Sciences (IUCS-CESPU), CRL, 4585-116 Gandra, Portugal
| | - Ricardo Silvestre
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal; (A.M.-F.); (R.S.)
- ICVS/3B’s—PT Government Associate Laboratory, 4710-057 Braga, Portugal
| | - Alexandra Viana da Costa
- University Institute of Health Sciences (IUCS-CESPU), 4585-116 Gandra, Portugal; (M.G.); (F.S.); (P.L.-J.); (A.V.d.C.)
- UCIBIO—Applied Molecular Biosciences Unit, Toxicologic Pathology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal
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18
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Dal-Fabbro R, Yu M, Mei L, Sasaki H, Schwendeman A, Bottino MC. Synthetic high-density lipoprotein (sHDL): a bioinspired nanotherapeutics for managing periapical bone inflammation. Int J Oral Sci 2024; 16:50. [PMID: 38956025 PMCID: PMC11219839 DOI: 10.1038/s41368-024-00316-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 06/06/2024] [Accepted: 06/11/2024] [Indexed: 07/04/2024] Open
Abstract
Apical periodontitis (AP) is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth (i.e., dental pulp tissue), resulting in inflammation and apical bone resorption affecting 50% of the worldwide population, with more than 15 million root canals performed annually in the United States. Current treatment involves cleaning and decontaminating the infected tissue with chemo-mechanical approaches and materials introduced years ago, such as calcium hydroxide, zinc oxide-eugenol, or even formalin products. Here, we present, for the first time, a nanotherapeutics based on using synthetic high-density lipoprotein (sHDL) as an innovative and safe strategy to manage dental bone inflammation. sHDL application in concentrations ranging from 25 µg to 100 µg/mL decreases nuclear factor Kappa B (NF-κB) activation promoted by an inflammatory stimulus (lipopolysaccharide, LPS). Moreover, sHDL at 500 µg/mL concentration markedly decreases in vitro osteoclastogenesis (P < 0.001), and inhibits IL-1α (P = 0.027), TNF-α (P = 0.004), and IL-6 (P < 0.001) production in an inflammatory state. Notably, sHDL strongly dampens the Toll-Like Receptor signaling pathway facing LPS stimulation, mainly by downregulating at least 3-fold the pro-inflammatory genes, such as Il1b, Il1a, Il6, Ptgs2, and Tnf. In vivo, the lipoprotein nanoparticle applied after NaOCl reduced bone resorption volume to (1.3 ± 0.05) mm3 and attenuated the inflammatory reaction after treatment to (1 090 ± 184) cells compared to non-treated animals that had (2.9 ± 0.6) mm3 (P = 0.012 3) and (2 443 ± 931) cells (P = 0.004), thus highlighting its promising clinical potential as an alternative therapeutic for managing dental bone inflammation.
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Affiliation(s)
- Renan Dal-Fabbro
- Department of Cariology, Restorative Sciences, and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, USA
| | - Minzhi Yu
- Department of Pharmaceutical Sciences, College of Pharmacy and Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA
| | - Ling Mei
- Department of Pharmaceutical Sciences, College of Pharmacy and Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA
| | - Hajime Sasaki
- Department of Cariology, Restorative Sciences, and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, USA
| | - Anna Schwendeman
- Department of Pharmaceutical Sciences, College of Pharmacy and Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA
| | - Marco C Bottino
- Department of Cariology, Restorative Sciences, and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
- Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, MI, USA.
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Barbero-Navarro I, Irigoyen-Camacho ME, Zepeda-Zepeda MA, Ribas-Perez D, Castaño-Seiquer A, Sofian-Pauliuc I. Understanding the Dynamics of Inflammatory Cytokines in Endodontic Diagnosis: A Systematic Review. Diagnostics (Basel) 2024; 14:1099. [PMID: 38893626 PMCID: PMC11171959 DOI: 10.3390/diagnostics14111099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 05/14/2024] [Accepted: 05/24/2024] [Indexed: 06/21/2024] Open
Abstract
The primary aim of this literature review is to delineate the key inflammatory cytokines involved in the pathophysiology of pulp inflammation. By elucidating the roles of these cytokines, a deeper comprehension of the distinct stages of inflamed pulp can be attained, thereby facilitating more accurate diagnostic strategies in endodontics. The PRISMA statement and Cochrane handbook were used for the search strategy. The keywords were created based on the review question using the PICO framework. The relevant studies were meticulously assessed according to predefined inclusion and exclusion criteria for this systematic review. A rigorous quality checklist was implemented to evaluate each included study, ensuring scrutiny for both quality and risk-of-bias assessments. The initial pilot search conducted on PubMed, Scopus, Cochrane, and WoS databases yielded 9 pertinent articles. Within these articles, multiple cytokines were identified and discussed as potential candidates for use in endodontic diagnosis, notably including IL-8, IL-6, TNF-α, and IL-2. These cytokines have been highlighted due to their significant roles in the inflammatory processes associated with pulp pathology. The identification of specific inflammatory cytokines holds promise for enhancing endodontic diagnostic procedures and exploring diverse treatment modalities. However, the current body of research in this area remains limited. Further comprehensive studies are warranted to fully elucidate the potential of cytokines in refining diagnostic techniques in endodontics.
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Affiliation(s)
| | | | | | - David Ribas-Perez
- Dental School, University of Seville, 41009 Seville, Spain; (I.B.-N.)
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20
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Knie LV, Leknes KN, Xue Y, Lie SA, Bunæs DF. Serum biomarker levels in smokers and non-smokers following periodontal therapy. A prospective cohort study. BMC Oral Health 2024; 24:463. [PMID: 38627806 PMCID: PMC11020793 DOI: 10.1186/s12903-024-04196-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Accepted: 03/27/2024] [Indexed: 04/19/2024] Open
Abstract
BACKGROUND To compare presence and levels of serum cytokines in smokers and non-smokers with periodontitis following periodontal therapy. METHODS Thirty heavy smokers and 30 non-smokers with stage III or IV periodontitis were included in this prospective cohort study. Clinical data and blood serum were collected at baseline (T0), after step I-III (T1), and after 12 months step IV periodontal therapy (T2). Cytokine IL-1β, IL-6, IL-8, TNF-α, IL-10, and IP-10 levels were measured using multiplex kit Bio-Plex Human Pro™ Assay. Linear regression models with cluster robust variance estimates to adjust for repeated observations were used to test intra- and intergroup levels for each marker, IL-6 and IL-8 defined as primary outcomes. RESULTS Clinical outcomes improved in both groups following therapy (p < 0.05). IL-6 levels increased with 75.0% from T0-T2 among smokers (p = 0.004). No significant intra- or intergroup differences were observed for IL-8. Higher levels of TNF-α (44.1%) and IL-10 (50.6%) were detected in smokers compared with non-smokers at T1 (p = 0.007 and p = 0.037, respectively). From T1-T2, differences in mean change over time for levels of TNF-α and IL-10 were observed in smokers compared with non-smokers (p = 0.005 and p = 0.008, respectively). CONCLUSION Upregulated levels of serum cytokines in smokers indicate a systemic effect of smoking following periodontal therapy. Differences in cytokine levels between smokers and non-smokers demonstrate a smoking induced modulation of specific systemic immunological responses in patients with severe periodontitis.
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Affiliation(s)
- Lorenz V Knie
- Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Årstadsveien 19, Bergen, N-5009, Norway
- Oral Health Centre of Expertise Rogaland, Stavanger, Norway
| | - Knut N Leknes
- Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Årstadsveien 19, Bergen, N-5009, Norway
| | - Ying Xue
- Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Årstadsveien 19, Bergen, N-5009, Norway
- Faculty of Health Sciences, Department of Clinical Dentistry, UiT The Arctic University of Norway, Tromsø, Norway
| | - Stein Atle Lie
- Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Årstadsveien 19, Bergen, N-5009, Norway
| | - Dagmar F Bunæs
- Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Årstadsveien 19, Bergen, N-5009, Norway.
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21
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Pinto KP, Fidalgo TKDS, de Lima CO, Lopes RT, Freitas-Fernandes LB, Valente AP, Sassone LM, Silva EJNL. Chronic alcohol and nicotine consumption as catalyst for systemic inflammatory storm and bone destruction in apical periodontitis. Int Endod J 2024; 57:178-194. [PMID: 37966374 DOI: 10.1111/iej.13994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 09/04/2023] [Accepted: 10/20/2023] [Indexed: 11/16/2023]
Abstract
AIM To assess the periapical alveolar bone pattern and the serum levels of proinflammatory cytokines, biochemical markers and metabolites in rats subjected to chronic alcohol and nicotine consumption and induced apical periodontitis. METHODOLOGY Twenty-eight male Wistar rats were divided into four groups: Control, Alcohol, Nicotine and Alcohol+Nicotine. The alcohol groups were exposed to self-administration of a 25% alcohol solution, while the other groups were given only filtered water. The nicotine groups received daily intraperitoneal injections of a nicotine solution (0.19 μL of nicotine/mL), whereas the other groups received saline solution. Periapical lesions were induced by exposing the pulps of the left mandibular first molars for 28 days. After euthanasia, the mandibles were removed and the percentage bone volume, bone mineral density, trabecular thickness, trabecular separation and trabecular number of the periapical bone were measured using micro-computed tomography images. Serum samples were collected for analysis of proinflammatory cytokines (IL-1β, IL-4, IL-6 and TNF-α), biochemical and metabolomic analysis. Statistical analysis was performed with a significance level of 5%. Nonparametric data were analysed using the Kruskal-Wallis test followed by Dunn's test, while one-way anova followed by Tukey's test was performed for parametric data. RESULTS The groups exposed to alcohol or nicotine consumption exhibited an altered bone pattern indicating lower bone density and higher levels of IL-1β, IL-6 and TNF-α compared to the Control group (p < .05). Significant differences were observed among the groups in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, cholesterol, triglycerides, urea, creatinine, albumin, uric acid, bilirubin and calcium. Metabolomic analysis revealed significant differences in glycine, phosphocholine, lysine, lactate, valine, pyruvate and lipids (CH2 CH2 CO), n(CH2 ) and n(CH3 ). Most of these parameters were even more altered in the simultaneous consumption of both substances compared to single consumption. CONCLUSION Alcohol and nicotine chronic consumption altered several metabolic markers, impaired liver and kidney function, increased the production of systemic proinflammatory mediators and harmed the periapical bone microarchitecture in the presence of apical periodontitis. The simultaneous consumption of alcohol and nicotine intensified these detrimental effects.
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Affiliation(s)
- Karem Paula Pinto
- Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Tatiana Kelly da Silva Fidalgo
- Department of Community and Preventive Dentistry, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | | | - Ricardo Tadeu Lopes
- Nuclear Engineering Program, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Liana Bastos Freitas-Fernandes
- National Center for Nuclear Magnetic Resonance, Medical Biochemistry, Rio de Janeiro Federal University, Rio de Janeiro, Brazil
| | - Ana Paula Valente
- National Center for Nuclear Magnetic Resonance, Medical Biochemistry, Rio de Janeiro Federal University, Rio de Janeiro, Brazil
| | - Luciana Moura Sassone
- Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
| | - Emmanuel João Nogueira Leal Silva
- Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
- Departament of Endodontics, Grande Rio University (UNIGRANRIO), Rio de Janeiro, Brazil
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22
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Pedrinha VF, Santos LM, Gonçalves CP, Garcia MT, Lameira OA, Queiroga CL, Marcucci MC, Shahbazi MA, Sharma PK, Junqueira JC, Sipert CR, de Andrade FB. Effects of natural antimicrobial compounds propolis and copaiba on periodontal ligament fibroblasts, molecular docking, and in vivo study in Galleria mellonella. Biomed Pharmacother 2024; 171:116139. [PMID: 38198959 DOI: 10.1016/j.biopha.2024.116139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 12/29/2023] [Accepted: 01/04/2024] [Indexed: 01/12/2024] Open
Abstract
Root canal treatment addresses infectious processes that require control. Occasionally, the radicular pulp is vital and inflamed, presenting a superficial infection. To preserve pulpal remnants, conservative procedures have gained favor, employing anti-inflammatory medications. This study investigated the effects of propolis (PRO), and copaiba oil-resin (COR) associated with hydrocortisone (H) and compared their impact to that of Otosporin® concerning cytotoxic and genotoxic activity, cytokine detection, and toxicity in the Galleria mellonella model. Human periodontal ligament fibroblasts (PDLFs) were exposed to drug concentrations and evaluated by the MTT assay. Associations were tested from concentrations that did not compromise cell density. Genotoxicity was evaluated through micronucleus counting, while cytokines IL-6 and TGF-β1 were detected in the cell supernatant using ELISA. Molecular docking simulations were conducted, considering the major compounds identified in PRO, COR, and H. Increasing concentrations of PRO and COR were assessed for acute toxicity in Galleria mellonella model. Cellular assays were analyzed using one-way ANOVA followed by Tukey tests, while larval survivals were evaluated using the Log-rank (Mantel-Cox) test (α = 0.05). PRO and COR promoted PDLFs proliferation, even in conjunction with H. No changes in cell metabolism were observed concerning cytokine levels. The tested materials induce the release of AT1R, proliferating the PDFLs through interactions. PRO and COR had low toxicity in larvae, suggesting safety at tested levels. These findings endorse the potential of PRO and COR in endodontics and present promising applications across medical domains, such as preventive strategies in inflammation, shedding light on their potential development into commercially available drugs.
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Affiliation(s)
- Victor Feliz Pedrinha
- Department of Operative Dentistry, Endodontics and Dental Materials, Bauru School of Dentistry, University of São Paulo (FOB - USP), Bauru, São Paulo, Brazil; Department of Biomaterials and Biomedical Technology (BBT), University Medical Center Groningen (UMCG), University of Groningen, Groningen, the Netherlands.
| | - Letícia Martins Santos
- Department of Operative Dentistry, School of Dentistry, University of São Paulo (FO-USP), São Paulo, Brazil
| | | | - Maíra Terra Garcia
- Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (UNESP), São José dos Campos, São Paulo, Brazil
| | | | - Carmen Lucia Queiroga
- State University of Campinas, CPQBA, Division of Phytochemistry, Campinas, São Paulo, Brazil
| | - Maria Cristina Marcucci
- Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (UNESP), São José dos Campos, São Paulo, Brazil
| | - Mohammad-Ali Shahbazi
- Department of Biomaterials and Biomedical Technology (BBT), University Medical Center Groningen (UMCG), University of Groningen, Groningen, the Netherlands
| | - Prashant Kumar Sharma
- Department of Biomaterials and Biomedical Technology (BBT), University Medical Center Groningen (UMCG), University of Groningen, Groningen, the Netherlands
| | - Juliana Campos Junqueira
- Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (UNESP), São José dos Campos, São Paulo, Brazil
| | - Carla Renata Sipert
- Department of Operative Dentistry, School of Dentistry, University of São Paulo (FO-USP), São Paulo, Brazil
| | - Flaviana Bombarda de Andrade
- Department of Operative Dentistry, Endodontics and Dental Materials, Bauru School of Dentistry, University of São Paulo (FOB - USP), Bauru, São Paulo, Brazil
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23
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Zheng X, Chen J, Liu J, Shi X, Li G, Shi Q, Zhang J, Li Y. The osteogenic effects of sappanchalcone in vitro and in vivo. J Periodontal Res 2024; 59:84-93. [PMID: 37814383 DOI: 10.1111/jre.13189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 08/22/2023] [Accepted: 09/01/2023] [Indexed: 10/11/2023]
Abstract
BACKGROUND AND OBJECTIVES The utilization of natural products to enhance the function of periodontal ligament cells (PDLCs) has emerged as a popular area of research. Recent investigations have demonstrated that sappanchalcone (SC) possesses pharmacological properties such as anti-inflammatory and osteoprotective effects. This study aims to explore the impact of SC on the in vivo and in vitro osteogenic differentiation ability of PDLCs. MATERIALS Cell proliferation was quantified using the CCK-8 assay, while gene expression levels were assessed through qRT-PCR analysis. Osteoblast differentiation capacity was evaluated by employing Alizarin red staining (ARS), alkaline phosphatase (ALP) staining and western blot (WB) analysis. A rat model of periodontitis was established utilizing the tether-wire method. Micro-CT imaging and hematoxylin and eosin (HE) staining were employed to evaluate alveolar bone resorption. Masson's trichrome staining was utilized to observe fiber alignment, whereas immunohistochemistry (IHC) techniques were applied for detecting osteogenic and inflammatory factors. RESULTS The results from the CCK-8 assay indicate no observed cytotoxicity for concentrations of 1, 5, or 10 nM for SC treatment (p < .05), while qRT-PCR analysis demonstrates a significant decrease in inflammatory factors such as MMP-1 and IL-6 with treatment by SC (p < .05). Additionally, western blotting reveals an increase in protein expression levels of Runx2 and OPN within PDLCs treated with SC compared to control groups (p < .05), which is further supported by ARS and ALP staining indicating an increase in mineralized nodules formation along with elevated ALP content within these cells following treatment with this compound (p < .05). Finally, both HE staining as well as micro-CT imaging suggest potential benefits associated with using this compound including slowing alveolar bone resorption while simultaneously promoting junctional epithelium proliferation. CONCLUSIONS Our in vitro and in vivo findings suggest that SC can effectively enhance the inflammatory response of PDLCs and promote their osteogenic differentiation ability under inflammatory conditions, indicating its potential as a promising therapeutic agent for improving periodontal inflammation and bone formation.
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Affiliation(s)
- Xiaodan Zheng
- Yunnan Key Laboratory of Stomatology, Kunming, China
- Department of Preventive Dentistry, Kunming Medical University School and Hospital of Stomatology, Kunming, China
| | - Jingqiu Chen
- Yunnan Key Laboratory of Stomatology, Kunming, China
- Department of Preventive Dentistry, Kunming Medical University School and Hospital of Stomatology, Kunming, China
| | - Juan Liu
- Department of Pediatric Dentistry, Kunming Medical University School and Hospital of Stomatology, Kunming, China
| | - Xiaoying Shi
- Yunnan Key Laboratory of Stomatology, Kunming, China
- Department of Prosthodontics Dentistry, Kunming Medical University School and Hospital of Stomatology, Kunming, China
| | - Gang Li
- Department of Prosthodontics Dentistry, Kunming Medical University School and Hospital of Stomatology, Kunming, China
| | - Qimeng Shi
- Yunnan Key Laboratory of Stomatology, Kunming, China
- Department of Preventive Dentistry, Kunming Medical University School and Hospital of Stomatology, Kunming, China
| | - Jun Zhang
- Yunnan Key Laboratory of Stomatology, Kunming, China
- Department of Pediatric Dentistry, Kunming Medical University School and Hospital of Stomatology, Kunming, China
| | - Yanhong Li
- Department of Preventive Dentistry, Kunming Medical University School and Hospital of Stomatology, Kunming, China
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Karataş E, Kul A, Camilleri J, Yonel Z. Association between rheumatoid arthritis and pulpal-periapical pathology: a systematic review. Clin Oral Investig 2023; 27:7019-7028. [PMID: 37828236 PMCID: PMC10713683 DOI: 10.1007/s00784-023-05305-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 10/03/2023] [Indexed: 10/14/2023]
Abstract
OBJECTIVES Rheumatoid arthritis (RA) is a debilitating disease where numerous pro-inflammatory cytokines have a proven role in its pathology. These cytokines are also involved in the pathogenesis of apical periodontitis (AP) where they have a pro-inflammatory role and induce bone resorption. Patients with RA may therefore be more prone to develop pulpal-periapical pathology (PPP). This study systematically reviewed the existing literature evaluating the association between RA and PPP. MATERIALS AND METHODS Studies including human participants with both RA and PPP were included. The search was performed in PubMed, Web of Science, and The Cochrane Library databases using keywords and Medical Subject Headings (MeSH) search terms. The risk of bias was assessed using Newcastle-Ottawa Quality Assessment Scale. The following parameters were extracted and analyzed by the reviewers; author, journal, year, design of the study, diagnostic criteria for periapical pathology, the association between rheumatoid arthritis and periapical pathology, and the evidence level. RESULTS The search identified 142 records. Inclusion criteria were as follows; studies in the English language, including human participants only, including patients with RA and PPP, cohort studies, cross-sectional studies, clinical trials, and case-control studies. According to the inclusion criteria, 5 studies were included in this systematic review. Three of the five studies reported significant association between RA and PPP. CONCLUSIONS Existing evidence suggests there may be an association between RA and PPP. CLINICAL RELEVANCE Clinicians should be aware that RA patients can be more prone to develop PPP which may result in a reduced quality of life.
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Affiliation(s)
- Ertugrul Karataş
- Department of Endodontics, Faculty of Dentistry, Atatürk University, Erzurum, Turkey
- School of Dentistry, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Ayhan Kul
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Atatürk University, Erzurum, Turkey
| | - Josette Camilleri
- School of Dentistry, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
| | - Zehra Yonel
- Periodontology Research Group, School of Dentistry, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
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Prasetyo EP, Sampoerno G, Juniarti DE, Cahyani F, Saraswati W, Kuntjoro M, Tjendronegoro E. Effect of Lipopolysaccharide-Induced Apical Periodontitis in Diabetes Mellitus Rats on Periapical Inflammation. Eur J Dent 2023; 17:1146-1152. [PMID: 36599453 PMCID: PMC10756800 DOI: 10.1055/s-0042-1758790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
OBJECTIVES To evaluate periapical inflammation through immunohistochemical analysis of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-a) expression resulting from lipopolysaccharide (LPS)-induced apical periodontitis in diabetes mellitus rats, observed at 14, 28, and 42 days. MATERIALS AND METHODS Diabetes model on rats was induced by streptozotocin (STZ). Fifteen rats were injected with low-dose STZ for 5 days and waited for 5 days until the blood glucose level was stable and measured above 300 mg/dL confirmed by a digital glucometer. LPS was used to induce apical periodontitis. After performing access cavity, pulpal and root canal extirpation was done on the right mandibular first molar's root canal space of rats, under anesthesia. LPS of 1 mg/mL dose was induced in the pulpal and root canal space. Apical periodontitis was expected 14 days afterward and then, the rats were randomly allocated to three groups. The first group was terminated 14 days after induction and used as control. The second group was observed 28 days after induction, and the third group was observed 42 days after induction. IL-6 and TNF-a expression was analyzed by immunohistochemistry on macrophages in the periapical area. STATISTICAL ANALYSIS Data were analyzed using one-way ANOVA and continued with the post hoc Tukey HSD test. Significance was considered if p < 0.05. RESULTS LPS induced apical periodontitis in diabetes mellitus rats at control (14 days), 28 and 42 days observation showed a significant increase in the expression of IL-6 and TNF-a. There were significant differences between the control and observed groups (p < 0.05). The expression of IL-6 in the apical area was not significant at 14 and 28 days (p > 0.05) but increased significantly at 42 days (p < 0.05). The expression of TNF-a in the apical area was significantly increased after 14 days (p < 0.05) and remained stable at 28 and 42 days (p > 0.05). CONCLUSIONS The periapical inflammation of LPS-induced apical periodontitis in diabetes mellitus rats increased macrophages' expression of IL-6 at 42 days and TNF-a at 28 days.
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Affiliation(s)
- Eric Priyo Prasetyo
- Department of Conservative Dentistry, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Galih Sampoerno
- Department of Conservative Dentistry, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Devi Eka Juniarti
- Department of Conservative Dentistry, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Febriastuti Cahyani
- Department of Conservative Dentistry, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Widya Saraswati
- Department of Conservative Dentistry, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Mefina Kuntjoro
- Department of Prosthodontics, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Evelyn Tjendronegoro
- Healthcare and Research, Irvine Medical Center, University of California, Irvine, California, United States
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Palafox-Sánchez CA, Cruz A, Salazar-Camarena DC, Gascón LG, Cintra LTA, Muñoz-Valle JF, García-Arellano S, Estrela C, Menchaca-Tapia PA. Evaluation of Serum Levels of Cytokines in Acute Apical Abscess: A Longitudinal Observational Study. J Endod 2023; 49:1090-1098. [PMID: 37423583 DOI: 10.1016/j.joen.2023.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 06/23/2023] [Accepted: 07/02/2023] [Indexed: 07/11/2023]
Abstract
INTRODUCTION Cytokine levels are related to the aethiopathogenia of acute apical abscesses (AAA); however, the specific cytokine profiles in these cases are unclear. This study aimed to investigate the changes in systemic cytokine levels in patients with AAA and trismus onset, postantibiotic treatment, and postroot canal disinfection. METHODS In total, 46 AAA patients with trismus and 32 control subjects were included. After seven days of antibiotic therapy, root canal disinfection was performed in the AAA patients. The serum levels of cytokines were evaluated at basal, seven, and 14 days after endodontic treatment. Quantification of cytokines from T helper (Th) 1, Th2, Th17, and regulatory T cells profiles was determined using the BioPlex MagPix system, and the obtained data were analyzed using SPSS statistical software (P < .05). RESULTS AAA patients showed higher tumor necrosis factor-alpha (TNF-α), interleukin (IL) -6, and IL-10 levels than control subjects, at basal measurement (P < .05); there were similar levels of interferon gamma, IL-1β, IL-4, and IL-17 between groups (P > .05). IL-6 and IL-10 levels decreased after antibiotic treatment (P < .05), which was also associated with clinical improvement in patients with AAA and trismus. Patients with AAA had a positive correlation with higher serum levels of IL-6 and IL-10. In addition, TNF-α levels decreased only after antibiotic and endodontic treatment. CONCLUSIONS In conclusion, patients with AAA had increased systemic serum levels of TNF-α, IL-6, and IL-10. Moreover, increased levels of IL-6 and IL-10 are associated with acute inflammatory symptoms. However, IL-6 and IL-10 levels decreased after antibiotic treatment, while TNF-α levels decreased after antibiotic and endodontic treatment.
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Affiliation(s)
- Claudia Azucena Palafox-Sánchez
- Instituto de Investigación en Ciencias Biomédicas (IICB), Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico; Grupo de Inmunología Molecular, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico
| | - Alvaro Cruz
- Instituto de Investigación en Ciencias Biomédicas (IICB), Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico; Posgrado de Endodoncia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico.
| | - Diana Celeste Salazar-Camarena
- Grupo de Inmunología Molecular, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico; Posgrado de Endodoncia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico
| | - Luis Gerardo Gascón
- Posgrado de Endodoncia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico
| | - Luciano Tavares Angelo Cintra
- Department of Preventive and Restorative Dentistry, School of Dentistry, São Paulo State University (UNESP), and School of Dentistry, Dental Assistance Center for Disabled Persons (CAOE) of the São Paulo State University (UNESP), Araçatuba, SP, Brazil
| | - José Francisco Muñoz-Valle
- Instituto de Investigación en Ciencias Biomédicas (IICB), Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico
| | - Samuel García-Arellano
- Instituto de Investigación en Ciencias Biomédicas (IICB), Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico
| | - Carlos Estrela
- Department of Stomatologic Sciences, School of Dentistry, Federal University of Goiás (UFG), Goiânia, GO, Brazil
| | - Paula Annahi Menchaca-Tapia
- Doctorado en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico
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Jia T, Yuan F, Tao J, Wang G, Zhang X, Zhang B, Li H. CRISPR/Cas13d targeting GZMA in PARs pathway regulates the function of osteoclasts in chronic apical periodontitis. Cell Mol Biol Lett 2023; 28:70. [PMID: 37626297 PMCID: PMC10464397 DOI: 10.1186/s11658-023-00477-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 07/17/2023] [Indexed: 08/27/2023] Open
Abstract
Chronic apical periodontitis is a prevalent oral disease characterized by bone loss, and its underlying mechanisms remain unclear. This study aimed to investigate the role and mechanism of the serine protease GZMA in osteoclasts during chronic apical periodontitis. To address this, we employed crRNA/Cas13d to inhibit GZMA expression and examined its impact on osteoclast behavior. Our findings revealed that GZMA plays a significant role in promoting osteoclast cell proliferation while inhibiting cell apoptosis. Additionally, the inhibition of GZMA led to a notable increase in miR-25-3p expression, which, in turn, downregulated the expression of TGF-β. Consequently, the reduction in TGF-β expression led to a decrease in PAR1 expression within the PARs pathway. These results suggest that GZMA might serve as a promising therapeutic target for the treatment of chronic apical periodontitis. Furthermore, our study highlights the potential of targeting GZMA using crRNA/Cas13d as a valuable approach for future therapeutic interventions.
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Affiliation(s)
- Tingting Jia
- Department of Stomatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Fang Yuan
- Department of Oncology, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Jingqiao Tao
- Department of Stomatology, Southern Medical Branch of PLA General Hospital, Beijing, China
| | - Gang Wang
- Medical School of Chinese PLA, Beijing, China
| | - Xianhua Zhang
- Department of Stomatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Bin Zhang
- Department of Stomatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China.
| | - Hongbo Li
- Department of Stomatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China.
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Yang H, Luo D, Yuan MJ, Yang JJ, Wang DS. Five-year outcomes of immediate implant placement for mandibular molars with and without chronic apical periodontitis: A retrospective study. World J Clin Cases 2023; 11:5218-5229. [DOI: 10.12998/wjcc.v11.i22.5218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 06/26/2023] [Accepted: 07/10/2023] [Indexed: 08/03/2023] Open
Abstract
BACKGROUND Most physicians consider molars with chronic apical periodontitis (CAP) lesions as contraindications for immediate implant placement. At the patient’s request, we perform immediate implant placement of the mandibular molars with CAP in clinical practice.
AIM To retrospectively analyze and compare the 5-year outcomes of immediate implant placement of the mandibular molars with CAP and those without obvious inflammation.
METHODS The clinical data of patients with immediate implant placement of the mandibular molars in the Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, from June 2015 to June 2017 were collected. The patients were divided into CAP (n = 52) and no-CAP (n = 45) groups. Changes in bone mineral density and bone mass around implants were analyzed 5 years after implant restoration.
RESULTS At 5 years after implantation, the peri-implant bone mineral density was 528.2 ± 78.8 Hounsfield unit (HU) in the CAP group and 562.6 ± 82.9 HU in the no-CAP group (P = 0.126). Marginal bone resorption around implants did not differ significantly between the two groups, including buccal (P = 0.268) or lingual (P = 0.526) resorption in the vertical direction or buccal (P = 0.428) or lingual (P = 0.560) resorption in the horizontal direction. Changes in the peri-implant jump space did not differ significantly between the two groups, including the buccal (P = 0.247) or lingual (P = 0.604) space in the vertical direction or buccal (P = 0.527) or lingual (P = 0.707) space in the horizontal direction. The gray value of cone-beam computed tomography measured using Image J software can reflect the bone mineral density. In the CAP area, the gray values of the bone tissue immediately and 5 years after implant placement differed significantly from those of the surrounding bone tissue (P < 0.01).
CONCLUSION The results of this study suggest that immediate implant placement of the mandibular molars with CAP can achieve satisfactory 5-year clinical results, without significant differences in the complications, survival rate, or bone tissue condition from the no-CAP mandibular molars.
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Affiliation(s)
- Hua Yang
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
- School of Stomatology, Qingdao University, Qingdao 266003, Shandong Province, China
| | - Dan Luo
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
- School of Stomatology, Qingdao University, Qingdao 266003, Shandong Province, China
| | - Mu-Jie Yuan
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
- School of Stomatology, Qingdao University, Qingdao 266003, Shandong Province, China
| | - Jian-Jun Yang
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
- School of Stomatology, Qingdao University, Qingdao 266003, Shandong Province, China
| | - Da-Shan Wang
- School of Stomatology, Qingdao University, Qingdao 266003, Shandong Province, China
- Department of Oral Implantology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
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Yang H, Luo D, Yuan MJ, Yang JJ, Wang DS. Five-year outcomes of immediate implant placement for mandibular molars with and without chronic apical periodontitis: A retrospective study. World J Clin Cases 2023; 11:5224-5235. [PMID: 37621586 PMCID: PMC10445073 DOI: 10.12998/wjcc.v11.i22.5224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 06/26/2023] [Accepted: 07/10/2023] [Indexed: 08/04/2023] Open
Abstract
BACKGROUND Most physicians consider molars with chronic apical periodontitis (CAP) lesions as contraindications for immediate implant placement. At the patient's request, we perform immediate implant placement of the mandibular molars with CAP in clinical practice. AIM To retrospectively analyze and compare the 5-year outcomes of immediate implant placement of the mandibular molars with CAP and those without obvious inflammation. METHODS The clinical data of patients with immediate implant placement of the mandibular molars in the Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, from June 2015 to June 2017 were collected. The patients were divided into CAP (n = 52) and no-CAP (n = 45) groups. Changes in bone mineral density and bone mass around implants were analyzed 5 years after implant restoration. RESULTS At 5 years after implantation, the peri-implant bone mineral density was 528.2 ± 78.8 Hounsfield unit (HU) in the CAP group and 562.6 ± 82.9 HU in the no-CAP group (P = 0.126). Marginal bone resorption around implants did not differ significantly between the two groups, including buccal (P = 0.268) or lingual (P = 0.526) resorption in the vertical direction or buccal (P = 0.428) or lingual (P = 0.560) resorption in the horizontal direction. Changes in the peri-implant jump space did not differ significantly between the two groups, including the buccal (P = 0.247) or lingual (P = 0.604) space in the vertical direction or buccal (P = 0.527) or lingual (P = 0.707) space in the horizontal direction. The gray value of cone-beam computed tomography measured using Image J software can reflect the bone mineral density. In the CAP area, the gray values of the bone tissue immediately and 5 years after implant placement differed significantly from those of the surrounding bone tissue (P < 0.01). CONCLUSION The results of this study suggest that immediate implant placement of the mandibular molars with CAP can achieve satisfactory 5-year clinical results, without significant differences in the complications, survival rate, or bone tissue condition from the no-CAP mandibular molars.
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Affiliation(s)
- Hua Yang
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
- School of Stomatology, Qingdao University, Qingdao 266003, Shandong Province, China
| | - Dan Luo
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
- School of Stomatology, Qingdao University, Qingdao 266003, Shandong Province, China
| | - Mu-Jie Yuan
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
- School of Stomatology, Qingdao University, Qingdao 266003, Shandong Province, China
| | - Jian-Jun Yang
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
- School of Stomatology, Qingdao University, Qingdao 266003, Shandong Province, China
| | - Da-Shan Wang
- School of Stomatology, Qingdao University, Qingdao 266003, Shandong Province, China
- Department of Oral Implantology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
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Adeodato CSR, Soares-Lima SC, Batista PV, Fagundes MCN, Camuzi D, Tavares SJO, Pinto LFR, Scelza MFZ. Interleukin 6 and Interleukin 1β hypomethylation and overexpression are common features of apical periodontitis: a case-control study with gingival tissue as control. Arch Oral Biol 2023; 150:105694. [PMID: 37043986 DOI: 10.1016/j.archoralbio.2023.105694] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 03/20/2023] [Accepted: 04/04/2023] [Indexed: 04/08/2023]
Abstract
OBJECTIVES Apical periodontitis is a periradicular tissue disorder that usually arises from infection by microorganisms in the root canal system resulting in local bone resorption. This usually involves the dysregulation of inflammatory mediators, which can be mediated by epigenetic mechanisms. Thus, the objective of this study was to evaluate Interleukin 6 (IL6) and Interleukin 1β (IL1β) and DNA methylation and gene expression levels in apical periodontitis. METHODS Gene expression was analyzed in 60 participants using quantitative polymerase chain reaction, while the methylation levels of IL6 and IL1β promoters were analyzed in 72 patients using pyrosequencing. All statistical analyzes were performed using the GraphPad Prism software version 8.0. The p value was considered statistically significant when < 0.05. RESULTS A significantly higher IL6 and IL1β expression levels were observed in cases relative to controls (fold-changes of 27.4 and 11.43, respectively, and p < 0.0001). By comparing the same groups, lower promoter methylation levels were observed for both genes in cases (methylation percentage delta relative to controls of -24.57% and -16.02%, respectively, and p < 0.0001). A significant inverse correlation between gene expression and promoter methylation was observed for both IL6 (p = 0.0002) and IL1β (p = 0.001). Neither IL6 expression nor promoter methylation were significantly associated with cases' age, smoking history, alcohol consumption history or sex. For IL1β, alcoholic cases showed lower methylation level relative to non-alcoholic cases (p = 0.01), while females showed higher methylation levels relative to males (p = 0.03). CONCLUSIONS Our data suggest a role for DNA methylation in IL6 and IL1β upregulation in apical periodontitis.
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Affiliation(s)
- Caroline Sousa Ribeiro Adeodato
- Post-graduation Program in Dentistry of Fluminense Federal University (UFF), Mario Santos Braga Street, no 28, 24020-140 Niteroi, RJ, Brazil
| | - Sheila Coelho Soares-Lima
- Molecular Carcinogenesis Program of National Cancer Institute (INCA), André Cavalcante Street, no 37, 20231-050 Rio de Janeiro, Brazil
| | - Paula Vieira Batista
- Molecular Carcinogenesis Program of National Cancer Institute (INCA), André Cavalcante Street, no 37, 20231-050 Rio de Janeiro, Brazil
| | - Marina Chianello Nicolau Fagundes
- Molecular Carcinogenesis Program of National Cancer Institute (INCA), André Cavalcante Street, no 37, 20231-050 Rio de Janeiro, Brazil
| | - Diego Camuzi
- Molecular Carcinogenesis Program of National Cancer Institute (INCA), André Cavalcante Street, no 37, 20231-050 Rio de Janeiro, Brazil
| | - Sandro Junio Oliveira Tavares
- Post-graduation Program in Dentistry of Fluminense Federal University (UFF), Mario Santos Braga Street, no 28, 24020-140 Niteroi, RJ, Brazil
| | - Luis Felipe Ribeiro Pinto
- Molecular Carcinogenesis Program of National Cancer Institute (INCA), André Cavalcante Street, no 37, 20231-050 Rio de Janeiro, Brazil; Biochemistry Department, Biology Institute, State University of Rio de Janeiro, Boulevard 28 de Setembro, 87 - Vila Isabel, 20511-010 Rio de Janeiro, Brazil
| | - Miriam Fatima Zaccaro Scelza
- Endodontics Department, Faculty of Dentistry, Fluminense Federal University (UFF), Mario Santos Braga Street, no 28, 24020-140 Niteroi, RJ, Brazil.
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Cui Y, Xie J, Cai L, Zhang D, Sun J, Zhou X. Berberine regulates bone metabolism in apical periodontitis by remodelling the extracellular matrix. Oral Dis 2023; 29:1184-1196. [PMID: 34874590 DOI: 10.1111/odi.14094] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 10/06/2021] [Accepted: 11/19/2021] [Indexed: 02/05/2023]
Abstract
OBJECTIVES The objectives of this study were to explore the role and related mechanism of berberine in repairing bone destruction in apical periodontics (AP). MATERIALS AND METHODS AP was established in 14 of 21 male Wistar rats (four weeks of age; 70-80 g) for 3 weeks. The canals were cleaned and administered berberine (2 mg/ml; n = 7) or calcium hydroxide (100 mg/ml; control; n = 7), followed by glass ionomer cement sealing. After 3 weeks, specimen collection followed by micro-computed tomography (μ-CT) and histological staining was performed, including haematoxylin and eosin staining, Masson's trichrome staining, tartrate-resistant acid phosphatase staining, immunohistochemistry and immunofluorescence histochemistry. RESULTS μ-CT showed that AP lesion volume reduced in the berberine group. Histopathology showed that berberine decreased the activity and number of osteoclasts but increased the expression of proteins related to osteoblast differentiation, including alkaline phosphatase and osterix. The immune cell, T cell, dendritic cell and macrophage counts were significantly decreased in the berberine group. In the berberine group, the expression of extracellular matrix-degraded proteases, metalloproteinases, was decreased; however, that of extracellular matrix-stable proteases, lysyl oxidases, was increased. CONCLUSIONS Berberine controlled the inflammatory response and regulated bone metabolism in AP by reducing metalloproteinase expression and increasing lysyl oxidases expression.
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Affiliation(s)
- Yujia Cui
- State Key Laboratory of Oral Diseases & National Clinical Center for Oral Diseases &, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Jing Xie
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Linyi Cai
- State Key Laboratory of Oral Diseases & National Clinical Center for Oral Diseases &, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Demao Zhang
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Jianxun Sun
- State Key Laboratory of Oral Diseases & National Clinical Center for Oral Diseases &, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xuedong Zhou
- State Key Laboratory of Oral Diseases & National Clinical Center for Oral Diseases &, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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32
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Wang S, Wang X, Bai F, Shi X, Zhou T, Li F. Effect of endodontic treatment on clinical outcome in type 2 diabetic patients with apical periodontitis. Heliyon 2023; 9:e13914. [PMID: 36925517 PMCID: PMC10011187 DOI: 10.1016/j.heliyon.2023.e13914] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 02/04/2023] [Accepted: 02/15/2023] [Indexed: 02/25/2023] Open
Abstract
Background Previous research has demonstrated that poor controlled diabetic showed higher prevalence of AP compared to well-controlled patients and endodontic treatment may improve metabolic control of patients with diabetes. The purpose of this trial was to clinically assess the effects of endodontic treatment on glycemic control in patients with type 2 diabetes mellitus (T2DM) and apical periodontitis (AP). Study design For present trial, AP + T2DM with patients insulin injection (Group1, G1,n = 65), AP + T2DM patients with hypoglycaemic agents (Group2, G2, n = 82), and AP patients without DM (Group3, G3, n = 86) were enrolled. After demographic characteristics and clinical examination were achieved, root canal treatment (RCT) was performed for each patient. Subjects were followed up at 2-week, 3- and 6-month. At each visit, blood samples were taken and clinical laboratory studies were performed. At 6-month follow-up, Periapical Index (PAI) score was used to assess the periapical status. Results A total of 237 subjects who met the including criteria were allocated in three groups and 223 subjects (94.1%) completed the treatments and the follow-up assessments. After treatment, taking PAI into consideration, both groups showed significant improvement of AP in each group (P < 0.05). Patients in G3 had a continued significant lower concentration of fasting plasma glucose (FPG) levels at follow-up (P < 0.05). A continued reduction of hemoglobin glycation (HbA1c) was observed in most of time points (P < 0.05). Throughout the trial, there are also significant changes in inflammatory factors in short-term. Conclusion Endodontic therapy improved AP healing, glycemic control and systemic inflammation in patients with T2DM and/or AP in each group. However, a continued reduction in inflammatory factors and decreasing of HbA1c in short-term could not be observed in this trial.
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Affiliation(s)
- Shengming Wang
- Department of Stomatology, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an City, China
| | - Xiaoqing Wang
- Department of Endocrinology and Metabolism, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an City, China
| | - Feng Bai
- Department of Endocrinology and Metabolism, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an City, China
| | - Xinlian Shi
- Department of Stomatology, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an City, China
| | - Tingting Zhou
- Department of Stomatology, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an City, China
| | - Fangfang Li
- Department of Stomatology, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an City, China
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Deng Z, Lin B, Liu F, Zhao W. Role of Enterococcus faecalis in refractory apical periodontitis: from pathogenicity to host cell response. J Oral Microbiol 2023; 15:2184924. [PMID: 36891193 PMCID: PMC9987735 DOI: 10.1080/20002297.2023.2184924] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2023] Open
Abstract
BACKGROUND Refractory apical periodontitis (RAP) is an oral infectious disease characterised by persistent inflammation, progressive alveolar bone destruction, and delayed bone healing. RAP has received increasing attention, because it cannot be cured after repeated root canal therapies. The aetiology of RAP is related to the complex interplay between the pathogen and its host. However, the exact pathogenesis of RAP remains unclarified and includes several factors, such as microorganism immunogenicity, host immunity and inflammation, and tissue destruction and repair. Enterococcus faecalis is the dominant pathogen involved in RAP, and has evolved multiple strategies to ensure survival, which cause persistent intraradicular and extraradicular infections. OBJECTIVE To review the crucial role of E. faecalis in the pathogenesis of RAP, and open new avenues for prevention and treatment of RAP. METHODS The PubMed and Web of Science databases were searched for pertinent publications, employing the search terms "Enterococcus faecalis", "refractory apical periodontitis", "persistent periapical periodontitis", "pathogenicity", "virulence", "biofilm formation", "dentine tubule", "immune cell", "macrophage", and "osteoblast". RESULTS AND CONCLUSION Besides its high pathogenicity due to various virulence mechanisms, E. faecalis modulates the macrophage and osteoblast responses, including regulated cell death, cell polarisation, cell differentiation, and inflammatory response. An in-depth understanding of the multifaceted host cell responses modulated by E. faecalis will help to design potential future therapeutic strategies and overcome the challenges of sustained infection and delayed tissue healing in RAP.
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Affiliation(s)
- Zilong Deng
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.,School of Stomatology, Southern Medical University, Guangzhou, China
| | - Binbin Lin
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.,School of Stomatology, Southern Medical University, Guangzhou, China
| | - Fan Liu
- School of Stomatology, Southern Medical University, Guangzhou, China
| | - Wanghong Zhao
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.,School of Stomatology, Southern Medical University, Guangzhou, China
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Merle CL, Wuestenfeld JC, Fenkse F, Wolfarth B, Haak R, Schmalz G, Ziebolz D. The Significance of Oral Inflammation in Elite Sports: A Narrative Review. Sports Med Int Open 2022; 6:E69-E79. [PMID: 36643596 PMCID: PMC9839431 DOI: 10.1055/a-1964-8538] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 09/01/2022] [Indexed: 12/27/2022] Open
Abstract
Recently, there has been intense discussion about sports dentistry and potential interactions between oral health and athletes' performance. This narrative review aims to provide a comprehensive overview of the available literature about oral inflammation in sports. For this purpose, it presents the most common types of oral inflammation (gingivitis, periodontitis, pericoronitis, apical periodontitis), and their prevalence in athletes. Both the impact of oral inflammation on performance and causes for oral inflammation in athletes are discussed by presenting current literature. Finally, international recommendations for dental care in sports are presented. Several studies stated a high prevalence of oral inflammation in athletes, especially of gingivitis (58-97%) and periodontitis (41%). Also, many athletes report oral pain (17-30%) and a negative impact of oral health on training (3-9%). Besides this, a systemic impact of oral inflammation is discussed: In periodontitis patients, blood parameters and physical fitness are changed. In athletes, associations between muscle injuries and poor oral health are reported. There are deficits in oral health behavior. Furthermore, systemic changes due to physical stress could influence oral tissues. Overall, complex bidirectional interactions between competitive sports and oral inflammation are possible. Regular dental examinations and prevention strategies should be implemented in sports.
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Affiliation(s)
- Cordula Leonie Merle
- Department of Prosthetic Dentistry, Universitätsklinikum Regensburg, Regensburg, Germany.,Department of Cariology, Endodontology and Periodontology, University of Leipzig Faculty of Medicine, Leipzig, Germany
| | - Jan C Wuestenfeld
- Department of Sports Medicine, Institute for Applied Scientific Training, Leipzig, Germany.,Department of Sports Medicine, Charité University Medicine, Berlin, Germany
| | - Fabian Fenkse
- Department of Oral, Craniomaxillofacial and Facial Plastic Surgery, University of Leipzig Faculty of Medicine, Leipzig, Germany
| | - Bernd Wolfarth
- Department of Sports Medicine, Institute for Applied Scientific Training, Leipzig, Germany.,Department of Sports Medicine, Charité University Medicine, Berlin, Germany.,Department of Oral, Craniomaxillofacial and Facial Plastic Surgery, University of Leipzig Faculty of Medicine, Leipzig, Germany
| | - Rainer Haak
- Department of Cariology, Endodontology and Periodontology, University of Leipzig Faculty of Medicine, Leipzig, Germany
| | - Gerhard Schmalz
- Department of Cariology, Endodontology and Periodontology, University of Leipzig Faculty of Medicine, Leipzig, Germany
| | - Dirk Ziebolz
- Department of Cariology, Endodontology and Periodontology, University of Leipzig Faculty of Medicine, Leipzig, Germany
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Bai Y, Wang C, Jiang H, Wang L, Li N, Zhang W, Liu H. Effects of hydrogen rich water and pure water on periodontal inflammatory factor level, oxidative stress level and oral flora: a systematic review and meta-analysis. ANNALS OF TRANSLATIONAL MEDICINE 2022; 10:1120. [PMID: 36388830 PMCID: PMC9652511 DOI: 10.21037/atm-22-4422] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 10/14/2022] [Indexed: 04/08/2025]
Abstract
BACKGROUND Hydrogen rich water (HRW) was used as an auxiliary treatment for periodontitis and peri-implantitis due to its good antioxidant properties. However, the stability of artificially added active hydrogen was far less than that of pure natural active hydrogen, which greatly reduced active hydrogen molecules number in HRW. Meanwhile, the effect of HRW was relatively slow. Finally, long-term drinking of HRW may cause abnormal liver function. Hence, this study sought to summarize and analyze the effects of HRW on oral inflammation and oral flora in various studies to determine whether HRW can be used to inhibit dental plaque formation and aliviate oral inflammation. METHODS Randomized controlled trials (RCTs) of HRW and pure water (PW) in the treatment of periodontal diseases published before March 2022 in the PubMed, Web of science, EMBASE, Cochrane, China Knowledge Resource Integrated, Wanfang, and Weipu databases were searched. Changes in the inflammatory factor levels, oxidative stress response, and oral flora were summarized and used as outcome indicators. The quality of included studies was assessed by Cochrane risk of bias assessment tool, and the standardized mean differences (SMD) and the 95% confidence intervals (CIs) were calculated using Review Manager 5.3. RESULTS In total, 17 studies, comprising 304 subjects, were included in this meta-analysis. Among them, 5 studies had a high risk of bias, and the rest had a certain risk of bias, thus, the total risk of bias was medium to low. The levels of interleukin (IL)-1β (SMD =-0.73; 95% CI: -1.29 to -0.18; P=0.009), tumor necrosis factor alpha (SMD =-2.51; 95% CI: -3.56 to -1.46; P<0.00001), IL-6 (SMD =-1.31; 95% CI: -1.96 to -0.67; P<0.0001), 8-hydroxyguanosine (SMD =-1.61; 95% CI: -2.35 to -0.87; P<0.0001), and reactive oxygen metabolites (SMD =-0.49; 95% CI: -0.91 to -0.06; P=0.02) in the HRW group decreased significantly, while the glutathione peroxidase level increased (SMD =2.5; 95% CI: 1.85 to 3.15; P<0.00001). Additionally, HRW was shown to effectively inhibit oral pathogenic bacteria activity (SMD =-0.91; 95% CI: -1.16 to -0.66; P<0.00001). CONCLUSIONS HRW effectively inhibits the inflammatory reaction, oxidative stress level, and bacterial proliferation activity in patients with periodontal disease.
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Affiliation(s)
- Yang Bai
- Department of Stomatology, the First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Chenglong Wang
- Department of Stomatology, the Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Hua Jiang
- Department of Stomatology, the First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Lin Wang
- Department of Stomatology, the First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Nan Li
- Department of Stomatology, the First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Wei Zhang
- Department of Stomatology, the First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Hongchen Liu
- Department of Stomatology, the First Medical Center, Chinese PLA General Hospital, Beijing, China
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In Vitro Evaluation of Five Newly Isolated Bacteriophages against E. faecalis Biofilm for Their Potential Use against Post-Treatment Apical Periodontitis. Pharmaceutics 2022; 14:pharmaceutics14091779. [PMID: 36145527 PMCID: PMC9503355 DOI: 10.3390/pharmaceutics14091779] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/22/2022] [Accepted: 08/22/2022] [Indexed: 11/17/2022] Open
Abstract
State-of-the-art treatment of root canal infection includes the use of mechanical debridement and chemical agents. This disinfection method is limited, and microorganisms can remain in the canal system. Enterococcus faecalis appears with a high prevalence in secondary and persistent root canal infections and can be linked to endodontic treatment failure due to its various resistance mechanisms. Here, we evaluated the activity of newly isolated bacteriophages against clinical isolates of E. faecalis (including one vancomycin- and gentamicin-resistant strain) as a single treatment or in combination with gentamicin and vancomycin. For the resistant strain, daptomycin and fosfomycin were tested. Sixteen E. faecalis strains were used to screen for the presence of bacteriophages in sewage. Five different bacteriophages were characterized in terms of virion morphology, host range and killing-kinetics against each E. faecalis host strain. To investigate the antibiofilm effect of antibiotic and phages, E. faecalis biofilm was grown on porous glass beads and treated with different antibiotic concentrations and with isolated bacteriophages alone or in staggered combinations. A strong biofilm reduction was observed when phages were combined with antibiotic, where combinations with gentamicin showed a better outcome compared to vancomycin. Regarding the resistant strain, daptomycin had a superior antibiofilm effect than fosfomycin.
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Kaval ME, Cakir B, Polatli E, Rençber S, Karavana SY, Nalbantsoy A, Güneri P. IL-1ß, IL-6 and TNF-α expression levels of macrophage cells induced by benzydamine hydrochloride, benzydamine hydrochloride with chitosan, calcium hydroxide and chlorhexidine medicaments: An ELISA study. Dent Mater J 2022; 41:545-551. [PMID: 35676045 DOI: 10.4012/dmj.2021-265] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
The aim of the present study was to evaluate IL-1ß, IL-6 and TNF-α expression levels of macrophage cells induced by benzydamine hydrochloride (BNZ), BNZ with chitosan, calcium hydroxide (CH) and chlorhexidine (CHX) medicaments. Half maximal inhibitory concentrations (IC50) were assessed on THP-1, Saos-2, and CRL-2014 cells using MTT assay. THP-1 cells were differentiated into macrophages with phorbol12-myristate13-acetate and activated with lipopolysaccharide. IL-1β, IL-6 and TNF-α levels in supernatants were determined using enzyme-linked immunosorbent assay (ELISA). The data were examined with one-way ANOVA and Tukey's multiple comparison test (p=0.05). At the selected concentrations, the cell viability was higher than 50% for chitosan and CH, whereas CHX presented lower IC50 values than BNZ and BNZ+chitosan. According to ELISA results, the lowest IL-1β, IL-6 and TNF-α values were observed with BNZ+Chitosan 50 µg/mL and BNZ 50 µg/mL. BNZ+chitosan 50 µg/mL combination has revealed promising anti-inflammatory effects. Nevertheless, these findings need to be examined in clinical conditions.
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Affiliation(s)
| | - Büşra Cakir
- Department of Bioengineering, Faculty of Engineering, Ege University
| | - Elifsu Polatli
- Department of Bioengineering, Faculty of Engineering, Ege University
| | - Seda Rençber
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Izmir Katip Celebi University
| | | | - Ayşe Nalbantsoy
- Department of Bioengineering, Faculty of Engineering, Ege University
| | - Pelin Güneri
- Department of Oral and Maxillofacial Radiology, School of Dentistry, Ege University
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Austah ON, Lillis KV, Akopian AN, Harris SE, Grinceviciute R, Diogenes A. Trigeminal neurons control immune-bone cell interaction and metabolism in apical periodontitis. Cell Mol Life Sci 2022; 79:330. [PMID: 35639178 PMCID: PMC9156470 DOI: 10.1007/s00018-022-04335-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/24/2022] [Accepted: 04/28/2022] [Indexed: 12/14/2022]
Abstract
Abstract Apical periodontitis (AP) is an inflammatory disease occurring following tooth infection with distinct osteolytic activity. Despite increasing evidence that sensory neurons participate in regulation of non-neuronal cells, their role in the development of AP is largely unknown. We hypothesized that trigeminal ganglia (TG) Nav1.8+ nociceptors regulate bone metabolism changes in response to AP. A selective ablation of nociceptive neurons in Nav1.8Cre/Diphtheria toxin A (DTA)Lox mouse line was used to evaluate the development and progression of AP using murine model of infection-induced AP. Ablation of Nav1.8+ nociceptors had earlier progression of AP with larger osteolytic lesions. Immunohistochemical and RNAscope analyses demonstrated greater number of macrophages, T-cells, osteoclast and osteoblast precursors and an increased RANKL:OPG ratio at earlier time points among Nav1.8Cre/ DTALox mice. There was an increased expression of IL-1α and IL-6 within lesions of nociceptor-ablated mice. Further, co-culture experiments demonstrated that TG neurons promoted osteoblast mineralization and inhibited osteoclastic function. The findings suggest that TG Nav1.8+ neurons contribute to modulation of the AP development by delaying the influx of immune cells, promoting osteoblastic differentiation, and decreasing osteoclastic activities. This newly uncovered mechanism could become a therapeutic strategy for the treatment of AP and minimize the persistence of osteolytic lesions in refractory cases. Graphical abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1007/s00018-022-04335-w.
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Affiliation(s)
- Obadah N Austah
- Department of Endodontics, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA.,Department of Endodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Katherine V Lillis
- Department of Endodontics, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA
| | - Armen N Akopian
- Department of Endodontics, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA
| | - Stephen E Harris
- Department of Periodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
| | - Ruta Grinceviciute
- Department of Endodontics, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA
| | - Anibal Diogenes
- Department of Endodontics, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA.
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Chachlioutaki K, Karavasili C, Adamoudi E, Tsitsos A, Economou V, Beltes C, Bouropoulos N, Katsamenis OL, Doherty R, Bakopoulou A, Fatouros DG. Electrospun Nanofiber Films Suppress Inflammation In Vitro and Eradicate Endodontic Bacterial Infection in an E. faecalis-Infected Ex Vivo Human Tooth Culture Model. ACS Biomater Sci Eng 2022; 8:2096-2110. [PMID: 35427110 DOI: 10.1021/acsbiomaterials.2c00150] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Treatment failure of endodontic infections and their concurrent inflammations is commonly associated with microbial persistence and reinfection, also stemming from the anatomical restrictions of the root canal system. Aiming to address the shortcomings of current treatment options, a fast-disintegrating nanofibrous film was developed for the intracanal coadministration of an antimicrobial (ZnO nanoparticles) and an anti-inflammatory (ketoprofen) agent. The electrospun films were fabricated based on polymers that dissolve rapidly to constitute the actives readily available at the site of action, aiming to eliminate both microbial infection and inflammation. The anti-inflammatory potency of the nanofiber films was assessed in an in vitro model of lipopolysaccharide (LPS)-stimulated RAW 264.7 cells after confirming their biocompatibility in the same cell line. The nanofiber films were found effective against Enterococcus faecalis, one of the most prominent pathogens inside the root canal space, both in vitro and ex vivo using a human tooth model experimentally infected with E. faecalis. The physical properties and antibacterial and anti-inflammatory potency of the proposed electrospun nanofiber films constitute a promising therapeutic module in the endodontic therapy of nonvital infected teeth. All manuscripts must be accompanied by an abstract. The abstract should briefly state the problem or purpose of the research, indicate the theoretical or experimental plan used, summarize the principal findings, and point out major conclusions.
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Affiliation(s)
- Konstantina Chachlioutaki
- Department of Pharmacy, Division of Pharmaceutical Technology, Aristotle University of Thessaloniki, Thessaloniki GR-54124, Greece
| | - Christina Karavasili
- Department of Pharmacy, Division of Pharmaceutical Technology, Aristotle University of Thessaloniki, Thessaloniki GR-54124, Greece
| | - Elisavet Adamoudi
- Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki GR-54124, Greece
| | - Anestis Tsitsos
- Laboratory of Hygiene of Foods of Animal Origin─Veterinary Public Health, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki GR-54124, Greece
| | - Vangelis Economou
- Laboratory of Hygiene of Foods of Animal Origin─Veterinary Public Health, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki GR-54124, Greece
| | - Charis Beltes
- Department of Endodontics, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki GR-54124, Greece
| | - Nikolaos Bouropoulos
- Department of Materials Science, University of Patras, Rio 26504, Patras, Greece.,Foundation for Research and Technology Hellas, Institute of Chemical Engineering and High Temperature Chemical Processes, Patras 26504, Greece
| | - Orestis L Katsamenis
- μ-VIS X-ray Imaging Centre, Faculty of Engineering and Physical Sciences, University of Southampton, Southampton SO17 1BJ, United Kingdom
| | - Regan Doherty
- Biomedical Imaging Unit, University Hospital Southampton NHS Trust, Southampton SO16 6YD, United Kingdom
| | - Athina Bakopoulou
- Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki GR-54124, Greece
| | - Dimitrios G Fatouros
- Department of Pharmacy, Division of Pharmaceutical Technology, Aristotle University of Thessaloniki, Thessaloniki GR-54124, Greece
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Li FC, Hussein H, Magalhaes M, Selvaganapathy PR, Kishen A. Deciphering Stem Cell from Apical Papilla - Macrophage Choreography using a Novel 3D Organoid System. J Endod 2022; 48:1063-1072.e7. [PMID: 35513088 DOI: 10.1016/j.joen.2022.04.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 04/18/2022] [Accepted: 04/18/2022] [Indexed: 01/01/2023]
Abstract
INTRODUCTION Immune cell - mesenchymal stem cell crosstalk modulates the process of repair and regeneration. In this study, a novel heterogenous cell containing matrix based three-dimensional (3D) tissue-construct was employed to study the interactions between stem cells from apical papilla (SCAP) and macrophage for a comprehensive understanding on the cellular signalling mechanisms guiding inflammation and repair. METHODS SCAP and macrophages were seeded with collagen in 3D printed molds to generate self-assembled tissue-constructs, which were exposed to three conditions: no stimulation, lipopolysaccharide (LPS), and interleukin-4 (IL-4) from 0 to 14 days. Specimens from each group were evaluated for cellular interactions, inflammatory mediators (IL-1β, TNF-α, MDC, MIP-1β, MCP-1, IL-6, IL-8, TGF-β1, IL-1RA, IL-10), expression of surface markers (CD80, 206), transcription factors (pSTAT1, pSTAT6) and SCAP differentiation markers (DSPP, DMP-1, and alizarin red) using confocal laser scanning microscopy and multiplex cytokine profiling from 2 to 14 days. RESULTS SCAP and macrophages displayed a cytokine-mediated interaction and differentiation characteristics. The increased pro-inflammatory cytokines/chemokines: IL-1β, TNF-α, MDC and MIP-1β in the earlier phase followed by the higher ratio of pSTAT6/pSTAT1 and decreased CD206 (p<0.05), indicated a distinct polarization behavior in macrophages during repair in LPS group. Conversely, the equal ratio of pSTAT6/pSTAT1, late increase in CD206 and amplified secretion of IL-1RA, IL-10 and TGF-β1 (p<0.05) in the anti-inflammatory environment, directed alternative macrophage polarization, promoting SCAP differentiation and tissue modeling in IL-4 group. CONCLUSIONS The novel 3D organoid system developed in this study allowed a comprehensive analysis of the SCAP-macrophage interactions during inflammation and healing, providing a deeper insight on the periapical dynamics of immature tooth.
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Affiliation(s)
- Fang-Chi Li
- Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada
| | - Hebatullah Hussein
- Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada; Faculty of Dentistry, Ain Shams University, Endodontics Department, Cairo, Egypt
| | - Marco Magalhaes
- Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada
| | - P Ravi Selvaganapathy
- Department of Mechanical Engineering, McMaster University, Hamilton, Ontario, Canada
| | - Anil Kishen
- Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
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Küçük M, Aksoy U, Özer Şehirli A. Possible protective effects of the Bmal1 gene and melatonin on the prognosis of apical periodontitis. Med Hypotheses 2022. [DOI: 10.1016/j.mehy.2022.110806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Şengül V, Güney Z, Kurgan Ş, Önder C, Serdar MA, Günhan M. Evaluation of salivary and serum methylated arginine metabolites and nitric oxide synthase in advanced periodontitis patients. Clin Oral Investig 2022; 26:5061-5070. [PMID: 35426000 DOI: 10.1007/s00784-022-04479-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 04/05/2022] [Indexed: 11/24/2022]
Abstract
OBJECTIVES Methylated arginine metabolites and nitric oxide synthase (NOS) play a critical role in regulating endothelial function. The aim of this study was to determine levels of NOS, and methylated arginine metabolites (ADMA, SDMA, homoarginine, arginine, and L-NMMA) and IL-6 in serum and saliva in patients with advanced periodontal diseases and identify their association with clinical parameters. MATERIALS AND METHODS The study consisted of two groups: healthy individuals (control: n = 24), and generalized Stage III Grade B periodontitis (P: n = 21). Clinical periodontal parameters (probing pocket depth, bleeding on probing, clinical attachment level) were recorded. IL 6 and NOS levels in saliva and serum were analyzed by enzyme-linked immunosorbent assay (ELISA). ADMA, SDMA, homoArg, arginine, and L-NMMA in saliva and serum were analyzed by liquid chromatography-mass spectrometry (LC MS/MS). RESULTS Clinical parameters were significantly higher in the periodontitis group (p < 0.001). In periodontitis group, NOS, ADMA, and arginine levels in saliva were statistically significantly higher than control group (p < 0.05). Serum levels of SDMA were statistically significantly lower, and IL-6 was statistically significantly higher in P group than C group (p < 0.05). ADMA, NOS, and arginine levels were significantly positive correlated with all clinical periodontal parameters (p < 0.05). CONCLUSIONS These findings suggest that there is a relationship between severity of periodontal disease and endothelial dysfunction by means of ADMA. Salivary ADMA may be related with periodontal inflammation. CLINICAL RELEVANCE ADMA levels in periodontal inflammation are associated with endothelial dysfunction. According to the results of our study, periodontal inflammation is effective on both local and systemic methylated arginine metabolites and nitric oxide synthase levels. This may shed light on the relationship between periodontal disease and systemic status.
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Affiliation(s)
- Volkan Şengül
- Department of Periodontology, Faculty of Dentistry, Ankara University, 06500-Cankaya, Ankara, Turkey
| | - Zeliha Güney
- Department of Periodontology, Faculty of Dentistry, Yozgat Bozok University, Yozgat, Turkey
| | - Şivge Kurgan
- Department of Periodontology, Faculty of Dentistry, Ankara University, 06500-Cankaya, Ankara, Turkey.
| | - Canan Önder
- Department of Periodontology, Faculty of Dentistry, Ankara University, 06500-Cankaya, Ankara, Turkey
| | - Muhittin A Serdar
- Department of Medical Biochemistry, School of Medicine, Acıbadem University, İstanbul, Turkey
| | - Meral Günhan
- Department of Periodontology, Faculty of Dentistry, Ankara University, 06500-Cankaya, Ankara, Turkey
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do Nascimento IV, Rodrigues MIQ, Isaias PHC, Barros‐Silva PG, Sousa FB, Nunes Alves APN, Mota MRL. Chronic systemic corticosteroid therapy influences the development of pulp necrosis and experimental apical periodontitis, exacerbating the inflammatory process and bone resorption in rats. Int Endod J 2022; 55:646-659. [DOI: 10.1111/iej.13724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 03/06/2022] [Accepted: 03/07/2022] [Indexed: 11/29/2022]
Affiliation(s)
- Isabelly Vidal do Nascimento
- Division of Oral Pathology Department of Dental Clinic Faculty of Pharmacy, Dentistry and Nursing Federal University of Ceará (UFC) Fortaleza, Ceará Brazil
| | - Maria Imaculada Queiroz Rodrigues
- Division of Oral Pathology Department of Dental Clinic Faculty of Pharmacy, Dentistry and Nursing Federal University of Ceará (UFC) Fortaleza, Ceará Brazil
| | - Pedro Henrique Chaves Isaias
- Division of Oral Pathology Department of Dental Clinic Faculty of Pharmacy, Dentistry and Nursing Federal University of Ceará (UFC) Fortaleza, Ceará Brazil
| | - Paulo Goberlânio Barros‐Silva
- Division of Oral Pathology Department of Dental Clinic Faculty of Pharmacy, Dentistry and Nursing Federal University of Ceará (UFC) Fortaleza, Ceará Brazil
| | - Fabricio Bitu Sousa
- Division of Oral Pathology Department of Dental Clinic Faculty of Pharmacy, Dentistry and Nursing Federal University of Ceará (UFC) Fortaleza, Ceará Brazil
| | - Ana Paula Negreiros Nunes Alves
- Division of Oral Pathology Department of Dental Clinic Faculty of Pharmacy, Dentistry and Nursing Federal University of Ceará (UFC) Fortaleza, Ceará Brazil
| | - Mário Rogério Lima Mota
- Division of Oral Pathology Department of Dental Clinic Faculty of Pharmacy, Dentistry and Nursing Federal University of Ceará (UFC) Fortaleza, Ceará Brazil
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Džopalić T, Tomić S, Bekić M, Vučević D, Mihajlović D, Eraković M, Čolić M. Ex vivo study of IL-6 expression and function in immune cell subsets from human periapical lesions. Int Endod J 2022; 55:480-494. [PMID: 35150455 DOI: 10.1111/iej.13704] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 01/28/2022] [Accepted: 02/05/2022] [Indexed: 11/29/2022]
Abstract
AIM Even though IL-6 is a key inflammatory cytokine in periapical lesions (PLs), its function in stable periapical disease is unknown. Therefore, the aim of this study was to investigate following: first, the ex vivo production of IL-6 by clinically different PLs; next, subsets of immune cells expressing IL-6 in PLs according to their inflammatory status and finally, modulatory effect of IL-6 on T-cell cytokine production in cell cultures. METHODOLOGY Inflammatory cells were isolated from a total of 95 human PLs. Detection of IL-6+ cells within the myeloid and lymphoid populations was performed by multicolour flow cytometry. ELISA and FlowCytomix Microbeads Assay were used to measure cytokine levels in culture supernatants. To study the role of IL-6 in PLs, mononuclear cells (MNC) from symptomatic (Sy) or asymptomatic (Asy) PLs were treated with IL-6 or Tocilizumab, an IL-6R blocking antibody. The differences between groups were tested by unpaired t-test, Mann-Whitney or Friedman tests. RESULTS The levels of IL-6 in PL MNC culture supernatants were significantly higher compared to total PL cells and PL granulocytes (p<0.001). MNC from Sy PLs produced significantly hihger levels of IL-6 than MNC from Asy PLs (p<0.001). Flow cytometry analysis showed that NKT cells, CD8+ T cells and M2 macrophages (MØ), were dominant IL-6+ cells, in contrast to CD4+ T cells. However, CD8+ and CD4+ T cells contributed the most to IL-6 production. IL-6hi producing MNC cultures had higher levels of Th1 (IFN-γ), Th17 (IL-17A), Tfh (IL-21) and RANKL, whereas Th2 (IL-4) and Tregs cytokines (IL-10, TGF-β) were lower, compared to IL-6low producing cultures. Exogenous IL-6 stimulated 17A, IL-21 and RANKL, independently of PL activation status, but decreased IFN-γ, IL-4 and IL-33 levels in IL-6hi producing cultures. Tocilizumab increased IL-10 and TGF-β in IL-6low producing cultures. All differences were p<0.05. CONCLUSIONS Most immune cells from Sy PLs expressed higher levels of IL-6 compared to Asy PLs, which correlated with IL-6 production in culture. Analysis of cytokines suggested a dominant pro-inflammatory T-cell response and osteodestructive function of IL-6 in PLs judging by Th17/Tfh cell activation, Tregs inhibition and increased RANKL/OPG ratio. Excessive IL-6 production decreased Th1/Th2 responses.
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Affiliation(s)
- T Džopalić
- University of Niš, Medical Faculty, Niš, Serbia.,University of Defense in Belgrade, Medical Faculty of the Military Medical Academy, Belgrade, Serbia
| | - S Tomić
- University of Belgrade, Institute for the Application of Nuclear Energy, Belgrade, Serbia
| | - M Bekić
- University of Belgrade, Institute for the Application of Nuclear Energy, Belgrade, Serbia
| | - D Vučević
- University of Defense in Belgrade, Medical Faculty of the Military Medical Academy, Belgrade, Serbia
| | - D Mihajlović
- University of Defense in Belgrade, Medical Faculty of the Military Medical Academy, Belgrade, Serbia
| | - M Eraković
- Clinic for Stomatology, Military Medical Academy, Belgrade, Serbia
| | - M Čolić
- University of Belgrade, Institute for the Application of Nuclear Energy, Belgrade, Serbia.,University of East Sarajevo, Medical Faculty Foča, Foča R. Srpska Bosnia and Herzegovina
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The evaluation of cytotoxicity and cytokine IL-6 production of root canal sealers with and without the incorporation of simvastatin: an invitro study. BMC Oral Health 2022; 22:6. [PMID: 35012572 PMCID: PMC8751161 DOI: 10.1186/s12903-022-02039-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 12/28/2021] [Indexed: 12/07/2022] Open
Abstract
Background Freshly mixed root canal sealers when proximate the periapical tissues, trigger varying degrees of cytotoxicity/inflammatory reactions. Simvastatin, a class of the drug statin, is a widely used cholesterol-lowering agent with additional anti-inflammatory activities. This study assessed the effects of simvastatin on cytotoxicity and the release of IL-6 (Interleukin-6) production when incorporated in zinc oxide eugenol and methacrylate resin-based sealers. Methods Experimental groups consisted of conventional zinc oxide eugenol and methacrylate based-EndoREZ sealers (ZE & ER respectively) and 0.5 mg/mL simvastatin incorporated sealers (ZES & ERS). L929 mouse fibroblast cells were exposed to freshly mixed experimental sealers and evaluated for cytotoxicity (MTT assay) and inflammation levels (inflammatory marker IL-6 for ELISA) at various time intervals (0h, 24h and 7th day). The values were compared to the cell control (CC; L929 cells alone) and solvent control (SC; L929 cells + DMSO) groups. All the experiments were conducted in triplicates and subjected to statistical analysis using IBM SPSS Statistics software. Non parametric tests were conducted using Kruskal-Wallis and Friedman tests for inter-group and intra-group comparisons respectively. Pairwise comparison was conducted by post hoc Dunn test followed by Bonferroni correction. P values < 0.05 were considered statistically significant. Results All the experimental groups (ZE, ER, ZES, ERS) exhibited varying degree of cytotoxicity and IL-6 expression compared to the control groups CC and SC. The cell viability for ZE and ER decreased on day 7 as compared to 24 h. ZES and ERS had higher viable cells (75.93% & 79.90%) compared to ZE and ER (54.39% & 57.84%) at all time periods. Increased expression of IL-6 was observed in ZE & ER (25.49 pg/mL & 23.14 pg/mL) when compared to simvastatin incorporated ZE & ER (ZES-12.70 pg/mL & ERS-14.68 pg/mL) at all time periods. Highest level of cytotoxicity and inflammation was observed in ZE compared to all the other groups on day 7. Conclusions Addition of 0.5 mg/mL of simvastatin to the sealers (ZES and ERS) decreased the cytotoxicity in the freshly mixed state and reduces their inflammatory effect.
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Teixeira QE, Ferreira DDC, da Silva AMP, Gonçalves LS, Pires FR, Carrouel F, Bourgeois D, Sufiawati I, Armada L. Aging as a Risk Factor on the Immunoexpression of Pro-Inflammatory IL-1β, IL-6 and TNF-α Cytokines in Chronic Apical Periodontitis Lesions. BIOLOGY 2021; 11:biology11010014. [PMID: 35053012 PMCID: PMC8772771 DOI: 10.3390/biology11010014] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 12/17/2021] [Accepted: 12/20/2021] [Indexed: 11/16/2022]
Abstract
Persistent inflammatory responses in the elderly may act as modifiers on the progression and repair of chronic apical periodontitis lesions (CAPLs). While the involvement of IL-1β, IL-6 and TNF-α in inflammatory responses and, particularly, in CAPL has been documented, their expression in elderly patients needs to be further characterized. Therefore, the purpose of this study was to evaluate and compare the expressions of pro-inflammatory cytokines in CAPL from elderly individuals with young/middle-aged individuals. Thirty CAPL (15 cysts and 15 granulomas) from elderly patients (>60 years) and 30 CAPL (15 cysts and 15 granuloma) from young/middle-aged individuals (20–56 years) were selected. Immunohistochemical reactions were performed against IL-1β, IL-6 and TNF-α. The slides were subdivided into five high-magnification fields and analyzed. The number of positive stains was evaluated for each antibody. There was no significant difference between the cytokines when the cysts and granuloma were compared in the two groups. In the young/middle-aged, only IL-1β showed a difference and was significantly higher in granulomas (p = 0.019). CAPL pro-inflammatory cytokine levels in the elderly were significantly higher than in young/middle-aged individuals (p < 0.05). The pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were significantly higher in CAPL in the elderly compared with the young/middle-aged group. Further elaborate research studies/analyses to elucidate the reasons for and consequences of inflammation in the elderly are recommended.
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Affiliation(s)
- Quésia Euclides Teixeira
- Postgraduate Program in Dentistry, Estácio de Sá University, Rio de Janeiro 22790-710, Brazil; (Q.E.T.); (D.d.C.F.); (A.M.P.d.S.); (L.S.G.); (F.R.P.)
| | - Dennis de Carvalho Ferreira
- Postgraduate Program in Dentistry, Estácio de Sá University, Rio de Janeiro 22790-710, Brazil; (Q.E.T.); (D.d.C.F.); (A.M.P.d.S.); (L.S.G.); (F.R.P.)
| | - Alexandre Marques Paes da Silva
- Postgraduate Program in Dentistry, Estácio de Sá University, Rio de Janeiro 22790-710, Brazil; (Q.E.T.); (D.d.C.F.); (A.M.P.d.S.); (L.S.G.); (F.R.P.)
| | - Lucio Souza Gonçalves
- Postgraduate Program in Dentistry, Estácio de Sá University, Rio de Janeiro 22790-710, Brazil; (Q.E.T.); (D.d.C.F.); (A.M.P.d.S.); (L.S.G.); (F.R.P.)
| | - Fabio Ramoa Pires
- Postgraduate Program in Dentistry, Estácio de Sá University, Rio de Janeiro 22790-710, Brazil; (Q.E.T.); (D.d.C.F.); (A.M.P.d.S.); (L.S.G.); (F.R.P.)
| | - Florence Carrouel
- Health, Systemic, Process (P2S), UR 4129 Research Unit, University Claude Bernard Lyon 1, University of Lyon, 69008 Lyon, France;
- Correspondence: (F.C.); (L.A.); Tel.: +55-21-2497-898 (L.A.)
| | - Denis Bourgeois
- Health, Systemic, Process (P2S), UR 4129 Research Unit, University Claude Bernard Lyon 1, University of Lyon, 69008 Lyon, France;
| | - Irna Sufiawati
- Department of Oral Medicine, Universitas Padjadjaran, Bandung 40132, Indonesia;
| | - Luciana Armada
- Postgraduate Program in Dentistry, Estácio de Sá University, Rio de Janeiro 22790-710, Brazil; (Q.E.T.); (D.d.C.F.); (A.M.P.d.S.); (L.S.G.); (F.R.P.)
- Correspondence: (F.C.); (L.A.); Tel.: +55-21-2497-898 (L.A.)
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Du Q, Yuan S, Zhao S, Fu D, Chen Y, Zhou Y, Cao Y, Gao Y, Xu X, Zhou X, He J. Coexistence of Candida albicans and Enterococcus faecalis increases biofilm virulence and periapical lesions in rats. BIOFOULING 2021; 37:964-974. [PMID: 34839774 DOI: 10.1080/08927014.2021.1993836] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The present study utilized an in vitro dual-species biofilm model and an in vivo rat post-treatment endodontic disease (PTED) model to investigate whether co-infection of Candida albicans and Enterococcus faecalis would aggravate periapical lesions. The results showed that co-culturing yielded a thicker and denser biofilm more tolerant to detrimental stresses compared with the mono-species biofilm, such as a starvation-alkalinity environment, mechanical shear force and bactericidal chemicals. Consistently, co-inoculation of E. faecalis and C. albicans significantly increased the extent of in vivo periapical lesions compared with mono-species infection. Specifically, coexistence of both microorganisms increased osteoclastic bone resorption and suppressed osteoblastic bone formation. The synergistic effects also up-regulated inflammatory cytokines including TNF-α and IL-6. In summary, coexistence of C. albicans and E. faecalis increased periapical lesions by enhanced biofilm virulence.
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Affiliation(s)
- Qian Du
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China.,Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, China
| | - Shasha Yuan
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China.,Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Shuangyuan Zhao
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China
| | - Di Fu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China
| | - Yifei Chen
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China
| | - Yuan Zhou
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China.,Department of Pediatrics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Yangpei Cao
- Woody L. Hunt School of Dental Medicine, Texas Tech University Health Sciences Center, EI Paso, TX, USA
| | - Yuan Gao
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China.,Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xin Xu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China.,Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xuedong Zhou
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China.,Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Jinzhi He
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China.,Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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Guan X, He Y, Wei Z, Shi C, Li Y, Zhao R, Pan L, Han Y, Hou T, Yang J. Crosstalk between Wnt/β-catenin signaling and NF-κB signaling contributes to apical periodontitis. Int Immunopharmacol 2021; 98:107843. [PMID: 34153668 DOI: 10.1016/j.intimp.2021.107843] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 05/21/2021] [Accepted: 05/31/2021] [Indexed: 12/19/2022]
Abstract
In physiology conditions, the crosstalk of signaling pathways has been considered to extend the functions of individual pathways and results in a more complex regulatory network. The Wnt3a/β-catenin and NF-κB signaling pathways have been demonstrated involving in apical periodontitis (AP). As AP progresses, ultimately causes tooth loss. In the present study, we investigate the contribution of the crosstalk between the Wnt3a/β-catenin and NF-κB signaling pathways to the development of AP. Clinically, utilizing 60 human AP and healthy tissues (30 samples for each group), we found that the expression levels of Wnt3a/β-catenin and NF-κB were elevated in the Ap tissues compared to that in the healthy group. To further study the roles of Wnt3a/β-catenin and NF-κB signaling pathways in the development of AP, and the contribution of the crosstalk between these two signaling pathways to AP, we established the AP animal model and observed that, first, both pathways are activated in the AP group compared to the control group. Interestingly, by immunoprecipitation and western blot experiments, we revealed that there is greater interaction between NF-κB (phorspho-p65) and β-catenin in AP tissues compared to the control tissues. Importantly, when the NF-κB signaling pathway was blocked by its inhibitor, pyrrolidine dithiocarbamate (PDTC), the activity of the Wnt3a/β-catenin signaling pathway was abolished, and consequently led to the attenuation of the inflammation response in LPS-induced human periodontal ligament cells (hPDLCs). Thus, our data indicate that the crosstalk between Wnt3a/β-catenin and NF-κB signaling pathway contributes to the development of AP, and provide a therapeutic strategy for the treatment of AP as well.
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Affiliation(s)
- Xiaoyue Guan
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China
| | - Yani He
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China
| | - Zhichen Wei
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China
| | - Chen Shi
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China
| | - Yingxue Li
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China
| | - Rui Zhao
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China
| | - Lifei Pan
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China
| | - Yue Han
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China
| | - Tiezhou Hou
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
| | - Jianmin Yang
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
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Plemmenos G, Evangeliou E, Polizogopoulos N, Chalazias A, Deligianni M, Piperi C. Central Regulatory Role of Cytokines in Periodontitis and Targeting Options. Curr Med Chem 2021; 28:3032-3058. [PMID: 32838709 DOI: 10.2174/0929867327666200824112732] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 07/23/2020] [Accepted: 07/24/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Periodontitis is an immune-inflammatory disease that leads to the progressive destruction of bone and connective tissue in the periodontal area. The cytokine network plays a primary role in tissue homeostasis, the recruitment of immune cells to control the pathogenic impact and the regulation of osteoclastic function, thus modulating the intensity and duration of the immune response. This review provides an update on the main cytokines implicated in the pathogenesis and progression of periodontitis and their targeting potential in order to enrich current treatment options. METHODS A structured search of bibliographic databases (PubMed, MEDLINE, Scopus) was performed for peer-reviewed cytokine studies focused on periodontitis the last ten years. A qualitative content analysis was performed in screened papers and a critical discussion of main findings is provided. RESULTS An altered cytokine profile has been detected in periodontitis patients and the interplay of pro-inflammatory and/or anti-inflammatory cytokines has been associated with disease pathogenesis. Among the most prominent pro-inflammatory cytokines, TNF-α, IL-1β, IL-17, IL-6 and the chemokines CXCL-6, CXCL-8 are overexpressed in periodontitis patients and correlate with disease progression. On the other hand, the anti-inflammatory IL-4 and IL- 11 levels are reduced while IL-12 and IFN-γ expression play a dual role in periodontal disease. Current periodontitis treatment strategies include selective antibiotics, antimicrobial photodynamic therapy and probiotics, which can modulate the cytokine network and when applied in combination with specific anti-cytokine agents can exert additional beneficial effects. CONCLUSION It is evident that cytokines play a central regulatory role in the inflammatory process and immune cell response that underlies bone destruction in periodontitis. Specific cytokine targeting should be considered as a complementary therapeutic scheme to current periodontal management.
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Affiliation(s)
- Grigorios Plemmenos
- School of Dentistry, National and Kapodistrian University of Athens, 2 Thivon Str, Goudi, 115 27 Athens, Greece
| | - Evangelos Evangeliou
- School of Dentistry, National and Kapodistrian University of Athens, 2 Thivon Str, Goudi, 115 27 Athens, Greece
| | - Nikolaos Polizogopoulos
- School of Dentistry, National and Kapodistrian University of Athens, 2 Thivon Str, Goudi, 115 27 Athens, Greece
| | - Andreas Chalazias
- School of Dentistry, National and Kapodistrian University of Athens, 2 Thivon Str, Goudi, 115 27 Athens, Greece
| | - Marianthi Deligianni
- School of Dentistry, National and Kapodistrian University of Athens, 2 Thivon Str, Goudi, 115 27 Athens, Greece
| | - Christina Piperi
- School of Dentistry, National and Kapodistrian University of Athens, 2 Thivon Str, Goudi, 115 27 Athens, Greece
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50
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Huang L, Wu H, Wu Y, Song F, Zhang L, Li Z, Sun H, Huang C. Pcsk9 Knockout Aggravated Experimental Apical Periodontitis via LDLR. J Dent Res 2021; 101:83-92. [PMID: 34036816 DOI: 10.1177/00220345211015128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Apical periodontitis (AP), an inflammatory lesion around the apex of tooth roots, is mostly caused by dental pulp infection. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a vital role in regulating cholesterol homeostasis by targeting low-density lipoprotein receptor (LDLR) and participates in bacterium-induced chronic periodontitis. However, the roles of PCSK9 in AP are unknown. Here, we investigated its role in AP by using Pcsk9-/- mice. Micro-computed tomography scanning and histological staining revealed that the periapical bone loss of Pcsk9-/- mice was greater than that of wild-type (WT) mice, and increased expression of inflammation-related factors tumor necrosis factor α (TNF-α) and interleukin (IL)-6 was also observed. Immunofluorescence staining and quantitative real-time polymerase chain reaction showed PCSK9 expression in bone marrow macrophages (BMMs) was increased after treatment with lipopolysaccharide (LPS). This finding was consistent with the in vivo results that the expression level of PCSK9 in exposed WT mice increased compared with that in unexposed WT mice. After LPS challenge, the expression levels of TNF-α, IL-1β, and IL-6 in BMMs were increased, and Pcsk9 knockout aggravated the expression of these inflammatory factors. The number of osteoclasts positive for tartrate-resistant acid phosphatase staining around the apical lesion in Pcsk9-/- mice was higher than that in WT mice. Then BMMs underwent the osteoclast differentiation. Pcsk9 knockout BMMs induced increased and larger osteoclasts. While this effect of Pcsk9 knockout was abolished by the addition of Ldlr small interfering RNA, revealing that Pcsk9 knockout increased osteoclastogenesis was dependent on the LDLR. Immunohistochemistry staining showed increased expression level of LDLR in exposed Pcsk9-/- periapical areas. In vitro experiments showed that LPS promoted the expression level of LDLR in Pcsk9-/- BMMs and increased osteoclast formation ability, indicating that LPS promoted the elevation of osteoclasteogenesis caused by the Pcsk9 knockout. In conclusion, Pcsk9 deficiency aggravated the inflammatory response and promoted the osteoclastogenesis in an LDLR-dependent manner in AP experimental mice.
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Affiliation(s)
- L Huang
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
| | - H Wu
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
| | - Y Wu
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
| | - F Song
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
| | - L Zhang
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
| | - Z Li
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
| | - H Sun
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
| | - C Huang
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
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