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Scrobota I, Tig IA, Marcu AO, Potra Cicalau GI, Sachelarie L, Iova G. Evaluation of Immunohistochemical Biomarkers in Diabetic Wistar Rats with Periodontal Disease. J Pers Med 2024; 14:527. [PMID: 38793109 PMCID: PMC11121950 DOI: 10.3390/jpm14050527] [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: 04/09/2024] [Revised: 05/11/2024] [Accepted: 05/13/2024] [Indexed: 05/26/2024] Open
Abstract
BACKGROUND The association of periodontal disease and diabetes is a subject of intense research in terms of etiopathology and treatment options. This research aimed to evaluate the modulation of the local inflammatory status by two natural extracts, curcumin (Cu) and rutin (R), in an experimentally induced diabetes and periodontal disease in Wistar rats. METHODS Fifty Wistar albino rats were randomly assigned to five groups: Control (C), Diabetes-associated Periodontal Disease (DP), Diabetes-associated Periodontal Disease treated with Curcumin (DPCu), Diabetes-associated Periodontal Disease treated with Rutin (DPR), and Diabetes-associated Periodontal Disease treated with both Curcumin and Rutin (DPCuR). Gingival samples were collected from all rats, and immunohistochemical markers CD3, CD20, and CD34 were evaluated to assess the local inflammatory infiltrate. Descriptive statistics were applied (SPSS24 Software, Armonk, NY, USA). RESULTS Rutin, alone or combined with Curcumin, reduced CD3-positive cell levels. Curcumin demonstrated superior efficacy in reducing CD20-positive cells. The combination of Curcumin and Rutin had the most important impact on both markers. Curcumin notably increased immature CD34-positive cell levels. CONCLUSIONS Curcumin and Rutin, either alone or together, hold potential for reducing local inflammation in diabetes-induced periodontal disease in Wistar rats.
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Affiliation(s)
- Ioana Scrobota
- Department of Dental Medicine, Faculty of Medicine and Pharmacy, University of Oradea, 1st Decembrie Street, 410073 Oradea, Romania; (I.S.); (I.A.T.); (G.I.P.C.); (G.I.)
| | - Ioan Andrei Tig
- Department of Dental Medicine, Faculty of Medicine and Pharmacy, University of Oradea, 1st Decembrie Street, 410073 Oradea, Romania; (I.S.); (I.A.T.); (G.I.P.C.); (G.I.)
| | - Andrea Olivia Marcu
- Preclinics Department, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania;
| | - Georgiana Ioana Potra Cicalau
- Department of Dental Medicine, Faculty of Medicine and Pharmacy, University of Oradea, 1st Decembrie Street, 410073 Oradea, Romania; (I.S.); (I.A.T.); (G.I.P.C.); (G.I.)
| | - Liliana Sachelarie
- Preclinics Department, Faculty of Medicine, Apollonia University, 700511 Iasi, Romania
| | - Gilda Iova
- Department of Dental Medicine, Faculty of Medicine and Pharmacy, University of Oradea, 1st Decembrie Street, 410073 Oradea, Romania; (I.S.); (I.A.T.); (G.I.P.C.); (G.I.)
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Liu J, Zhang B, Zhu G, Liu C, Wang S, Zhao Z. Discovering genetic linkage between periodontitis and type 1 diabetes: A bioinformatics study. Front Genet 2023; 14:1147819. [PMID: 37051594 PMCID: PMC10083320 DOI: 10.3389/fgene.2023.1147819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 03/15/2023] [Indexed: 03/29/2023] Open
Abstract
Background: Relationship between periodontitis (PD) and type 1 diabetes (T1D) has been reported, but the detailed pathogenesis requires further elucidation. This study aimed to reveal the genetic linkage between PD and T1D through bioinformatics analysis, thereby providing novel insights into scientific research and clinical treatment of the two diseases.Methods: PD-related datasets (GSE10334, GSE16134, GSE23586) and T1D-related datasets(GSE162689)were downloaded from NCBI Gene Expression Omnibus (GEO). Following batch correction and merging of PD-related datasets as one cohort, differential expression analysis was performed (adjusted p-value <0.05 and ∣log2 fold change| > 0.5), and common differentially expressed genes (DEGs) between PD and T1D were extracted. Functional enrichment analysis was conducted via Metascape website. The protein-protein interaction (PPI) network of common DEGs was generated in The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Hub genes were selected by Cytoscape software and validated by receiver operating characteristic (ROC) curve analysis.Results: 59 common DEGs of PD and T1D were identified. Among these DEGs, 23 genes were commonly upregulated, and 36 genes were commonly downregulated in both PD- and T1D-related cohorts. Functional enrichment analysis indicated that common DEGs were mainly enriched in tube morphogenesis, supramolecular fiber organization, 9 + 0 non-motile cilium, plasma membrane bounded cell projection assembly, glomerulus development, enzyme-linked receptor protein signaling pathway, endochondral bone morphogenesis, positive regulation of kinase activity, cell projection membrane and regulation of lipid metabolic process. After PPI construction and modules selection, 6 hub genes (CD34, EGR1, BBS7, FMOD, IGF2, TXN) were screened out and expected to be critical in linking PD and T1D. ROC analysis showed that the AUC values of hub genes were all greater than 70% in PD-related cohort and greater than 60% in T1D-related datasets.Conclusion: Shared molecular mechanisms between PD and T1D were revealed in this study, and 6 hub genes were identified as potential targets in treating PD and T1D.
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Affiliation(s)
- Junqi Liu
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Bo Zhang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Guanyin Zhu
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Chenlu Liu
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Shuangcheng Wang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Zhihe Zhao
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- *Correspondence: Zhihe Zhao,
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Okić-Đorđević I, Obradović H, Kukolj T, Petrović A, Mojsilović S, Bugarski D, Jauković A. Dental mesenchymal stromal/stem cells in different microenvironments— implications in regenerative therapy. World J Stem Cells 2021; 13:1863-1880. [PMID: 35069987 PMCID: PMC8727232 DOI: 10.4252/wjsc.v13.i12.1863] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/15/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Current research data reveal microenvironment as a significant modifier of physical functions, pathologic changes, as well as the therapeutic effects of stem cells. When comparing regeneration potential of various stem cell types used for cytotherapy and tissue engineering, mesenchymal stem cells (MSCs) are currently the most attractive cell source for bone and tooth regeneration due to their differentiation and immunomodulatory potential and lack of ethical issues associated with their use. The microenvironment of donors and recipients selected in cytotherapy plays a crucial role in regenerative potential of transplanted MSCs, indicating interactions of cells with their microenvironment indispensable in MSC-mediated bone and dental regeneration. Since a variety of MSC populations have been procured from different parts of the tooth and tooth-supporting tissues, MSCs of dental origin and their achievements in capacity to reconstitute various dental tissues have gained attention of many research groups over the years. This review discusses recent advances in comparative analyses of dental MSC regeneration potential with regards to their tissue origin and specific microenvironmental conditions, giving additional insight into the current clinical application of these cells.
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Affiliation(s)
- Ivana Okić-Đorđević
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Hristina Obradović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Tamara Kukolj
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Anđelija Petrović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Slavko Mojsilović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Diana Bugarski
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Aleksandra Jauković
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
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Luong A, Tawfik AN, Islamoglu H, Gobriel HS, Ali N, Ansari P, Shah R, Hung T, Patel T, Henson B, Thankam F, Lewis J, Mintline M, Boehm T, Tumur Z, Seleem D. Periodontitis and diabetes mellitus co-morbidity: A molecular dialogue. J Oral Biosci 2021; 63:360-369. [PMID: 34728373 DOI: 10.1016/j.job.2021.10.006] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 10/21/2021] [Accepted: 10/26/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) and periodontitis are two biologically linked diseases that often coexist in complex interaction. While periodontitis may lead to insulin receptor desensitization, diabetes may increase the expression of inflammatory cytokines, such as Tumor Necrosis Factor-α (TNF-α) and Interleukin 6 (IL-6), in the gingival crevicular fluid and activate osteoclasts via Receptor activator of nuclear factor kappa-Β ligand (RANK-L) production, leading to bone resorption. However, the association between the two diseases processes, where one may exacerbate the progression of the other, is unclear. In addition, both diseases have similar mechanistic themes, such as chronic inflammation and oxidative stress. This review aimed to investigate the pathophysiological and molecular mechanisms underlying T2DM and periodontitis. HIGHLIGHT Uncontrolled diabetes is often associated with severe periodontitis, measured by clinical attachment loss. Alteration in the oral microbiome composition, which may activate the host inflammatory response and lead to irreversible oxidative stress, is a common finding in both diseases. An understanding of the molecular crosstalk between the two disease processes is crucial for developing therapeutic targets that inhibit bone resorption and halt the progression of periodontitis in patients with diabetes. CONCLUSION The Oral microbiome composition in T2DM and periodontitis shifts toward dysbiosis, favoring bacterial pathogens, such as Fusobacteria and Porphyromonas species. Both conditions are marked by pro-inflammatory immune activity via the activation of Interleukin 17 (IL-17), Interleukin 1 (IL-1), TNF-α, and Nuclear Factor Kappa Beta (NF-κB). Common molecular crosstalk signaling appears to involve advanced glycation end products (AGEs) and oxidative stress. Thus, future drug targets are multifactorial, ranging from modulatory of host inflammatory response to preventing the accumulation of AGEs and oxidative free radicals.
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Affiliation(s)
- Anthony Luong
- College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA
| | - Andy Nassif Tawfik
- College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA
| | - Hicret Islamoglu
- College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA
| | - Hanaa Selim Gobriel
- College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA
| | - Nada Ali
- College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA
| | - Pouya Ansari
- College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA
| | - Ruchita Shah
- College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA
| | - Tiffany Hung
- College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA
| | - Tanusha Patel
- College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA
| | - Bradley Henson
- College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA
| | - Finosh Thankam
- College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA
| | - Jill Lewis
- College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA
| | - Mark Mintline
- College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA
| | - Tobias Boehm
- College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA
| | - Zohra Tumur
- College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA
| | - Dalia Seleem
- College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA.
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Silva H. Tobacco Use and Periodontal Disease-The Role of Microvascular Dysfunction. BIOLOGY 2021; 10:441. [PMID: 34067557 PMCID: PMC8156280 DOI: 10.3390/biology10050441] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 05/05/2021] [Accepted: 05/07/2021] [Indexed: 12/30/2022]
Abstract
Periodontal disease consists in highly prevalent wide-ranging inflammatory conditions that affect the supporting apparatus of teeth. Tobacco use is the most important risk factor for periodontal disease as it increases disease severity and periodontal surgery complications. Tobacco use is harmful for the vasculature by causing microvascular dysfunction, which is known to negatively affect periodontal disease. To the author's knowledge this paper is the first comprehensive review on the mechanisms by which tobacco use affects oral microcirculation and impacts the pathophysiology of periodontal disease. In healthy subjects, acute nicotine administration or tobacco use (smoking/smokeless forms) increases the blood flow in the oral mucosa due to local irritation and increased blood pressure, which overcome neural- and endocrine-mediated vasoconstriction. Chronic tobacco smokers display an increased gingival microvascular density, which is attributed to an increased capillary recruitment, however, these microcirculatory units show higher tortuosity and lower caliber. These morphological changes, together with the repetitive vasoconstrictive insults, contribute to lower gingival perfusion in chronic smokers and do not completely regress upon smoking cessation. In periodontal disease there is considerable gingival inflammation and angiogenesis in non-smokers which, in chronic smokers, are considerably suppressed, in part due to local immune suppression and oxidative stress. Tobacco exposure, irrespective of the form of use, causes long-term microvascular dysfunction that increases the risk of complications due to the natural disease course or secondary therapeutic strategies.
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Affiliation(s)
- Henrique Silva
- Informetrics Research Group, Ton Duc Thang University, Ho Chi Minh City 758307, Vietnam;
- Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City 758307, Vietnam
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Vascular Endothelial Growth Factor: A Translational View in Oral Non-Communicable Diseases. Biomolecules 2021; 11:biom11010085. [PMID: 33445558 PMCID: PMC7826734 DOI: 10.3390/biom11010085] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 01/08/2021] [Accepted: 01/08/2021] [Indexed: 02/06/2023] Open
Abstract
Vascular endothelial growth factors (VEGFs) are vital regulators of angiogenesis that are expressed in response to soluble mediators, such as cytokines and growth factors. Their physiologic functions include blood vessel formation, regulation of vascular permeability, stem cell and monocyte/macrophage recruitment and maintenance of bone homeostasis and repair. In addition, angiogenesis plays a pivotal role in chronic pathologic conditions, such as tumorigenesis, inflammatory immune diseases and bone loss. According to their prevalence, morbidity and mortality, inflammatory diseases affecting periodontal tissues and oral cancer are relevant non-communicable diseases. Whereas oral squamous cell carcinoma (OSCC) is considered one of the most common cancers worldwide, destructive inflammatory periodontal diseases, on the other hand, are amongst the most prevalent chronic inflammatory conditions affecting humans and also represent the main cause of tooth loss in adults. In the recent years, while knowledge regarding the role of VEGF signaling in common oral diseases is expanding, new potential translational applications emerge. In the present narrative review we aim to explore the role of VEGF signaling in oral cancer and destructive periodontal inflammatory diseases, with emphasis in its translational applications as potential biomarkers and therapeutic targets.
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Rifai M, Aoun G, Majzoub Z. Evaluation of the Papillary Gingival Vasculature in Smokers and Nonsmokers with Chronic Periodontitis: A Clinical In Vivo Study. J Int Soc Prev Community Dent 2020; 10:368-375. [PMID: 32802785 PMCID: PMC7402256 DOI: 10.4103/jispcd.jispcd_134_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 04/07/2020] [Accepted: 04/14/2020] [Indexed: 11/29/2022] Open
Abstract
AIM Cigarette smoking has been recognized as an important risk factor in periodontal diseases. One of the suggested mechanisms behind this association is that nicotine alters the microcirculation and causes vasoconstriction and reduced blood flow through the periodontal tissues. Scarce information is currently available relative to the microvascular alterations associated with smoking and the distribution of capillaries through the various areas of the gingival tissues. The aims of this study were to assess, in human interproximal gingival biopsies, the number and diameter of gingival capillaries in periodontally affected smokers and nonsmokers using the CD34 immunohistochemical staining method. The pattern of distribution of vessels in the different areas of the gingival tissues was also assessed. MATERIALS AND METHODS Systemically healthy patients with moderate chronic periodontitis and ranging in age between 30 and 60 years were recruited for the study from the patient population attending the Periodontology Department of the Faculty of Dental Medicine at the Lebanese University of Beirut. The patients were selected to have a group of 10 patients (Group SP) of smokers (>10 cigarettes/day for the last 10 years) and a second group (Group NP) consisting of nonsmoking periodontally affected patients. Three to four weeks following initial preparation, one interproximal gingival biopsy was obtained from each patient. Immunohistochemical staining with CD34 mouse monoclonal antibody was used to identify the endothelial cells of the blood vessels within each sample. Twelve biopsy samples (five in Group NP and seven in Group SP) were chosen for the measurement of the number and diameter of vessels in three regions of the connective tissue of the biopsy under a blinded protocol. RESULTS In the two groups, the quantitative distribution of small, medium, and large vessels followed a similar trend with the number of small vessels being significantly greater than both medium and large vessels. Small vessels prevailed in the peripheral regions, whereas large vessels were more abundant in the deeper connective tissue areas. The total number of vessels seemed unaffected by chronic cigarette smoking in both groups in the entire biopsy area and in the separate connective tissue regions. Quantitative alteration in the total number of gingival capillaries was not observed in chronic smokers. A redistribution of small and large vessels in the superficial and deeper connective tissue areas of the gingival papilla was noted as a result of smoking in periodontal patients. CONCLUSION The quantitative distribution of small, medium, and large vessels follows a similar trend with the content in small vessels being significantly more important than both medium and large vessels. Smoking and periodontitis result in a redistribution of small and large vessels in the superficial and deeper connective tissue areas of the gingival papilla compared to nonsmoking periodontal patients. The significance and clinical implications of such rearrangement of vasculature within the gingival tissue need to be further investigated.
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Affiliation(s)
- Mohamad Rifai
- Department of Periodontics, Faculty of Dental Medicine, Lebanese University, Beirut, Lebanon
| | - Georges Aoun
- Department of Oral Medicine and Maxillofacial Radiology, Faculty of Dental Medicine, Lebanese University, Beirut, Lebanon
| | - Zeina Majzoub
- Department of Periodontics and Research, Faculty of Dental Medicine, Lebanese University, Beirut, Lebanon
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Gonçalves PGP, Lourenço SIM, de Vasconcelos Gurgel BC. Immunohistochemical study of CD34 and podoplanin in periodontal disease. J Periodontal Res 2019; 54:349-355. [PMID: 30656679 DOI: 10.1111/jre.12635] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Revised: 11/18/2018] [Accepted: 12/02/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND OBJECTIVE The aim of this study was to evaluate the angiogenesis and lymphangiogenesis in gingival tissue biopsy specimens of individuals with clinically healthy gingiva, chronic gingivitis, and chronic periodontitis (n = 30 per clinical condition). MATERIAL AND METHODS Histological sections were stained using hematoxylin and eosin as well as immunohistochemically with hematopoietic progenitor cell antigen CD34 and podoplanin (PDPN) antibodies to evaluate the microvascular count, area, and perimeter of blood and lymphatic vessels, respectively. RESULTS The results revealed a correlation between the microvascular count of blood and lymphatic vessels (P = 0.03; however, in individuals with chronic periodontitis, fewer lymphatic vessels were present than in the clinically healthy gingival tissue (P = 0.01), which was not observed in the case of microvascular area and perimeter. Podoplanin labeling was present in the epithelium, and the intensity of labeling was positively correlated to the intensity of the inflammatory infiltrate (P = 0.03). CONCLUSION In this study, we concluded that an increase in the number of blood and lymphatic vessels was not observed in bouth gingivitis and periodontitis samples. Podoplanin expression is highly associated with an increased inflammatory infiltration suggesting that PDPN might play an additional role in periodontal disease, other than solely as a lymphangiogenesis marker.
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