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Terakawa H, Kawarai Y, Tajiri I, Inage K, Suzuki-Narita M, Takeuchi J, Hirasawa R, Hagiwara S, Nakamura J, Ohtori S. Impact of Intra-Articular Diclofenac Etalhyaluronate on Pain and Osteoarthritic Changes in Advanced and End-Stage Hip Osteoarthritis. J Orthop Res 2025. [PMID: 40235431 DOI: 10.1002/jor.26088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 03/22/2025] [Accepted: 03/31/2025] [Indexed: 04/17/2025]
Abstract
Diclofenac etalhyaluronate combines the sustained-release properties of diclofenac with the therapeutic benefits of hyaluronic acid, providing extended analgesic effects for osteoarthritis management. This study investigated the effects of diclofenac etalhyaluronate and subsequent osteoarthritic changes in rat models of advanced and end-stage osteoarthritis. Monosodium iodoacetate (0.5 or 2.0 mg) was injected directly into the right hip joint of rats (n = 8 rats/group) using a posterior approach to induce osteoarthritis. Four weeks after monosodium iodoacetate administration, diclofenac etalhyaluronate (0.25 mg/25 µL) or 25 µL saline was administered in the same way. Pain behavior, number of microglia in the dorsal horn of the spinal cord, radiological features on microcomputed tomography, and histology of the hip joint were evaluated. Administration of diclofenac etalhyaluronate increased the pain threshold and reduced the number of microglia in the dorsal horn of the spinal cord in both models. However, radiological and histological examinations did not detect significant arthritic changes in either group that received diclofenac etalhyaluronate. Intra-articular administration, therefore, contributes to pain relief and improvement of central sensitization in advanced and end-stage osteoarthritis of the hip without subsequent progression of osteoarthritis. These findings highlight the potential of intra-articular administration of diclofenac etalhyaluronate as a conservative treatment option for advanced and end-stage hip osteoarthritis, particularly for patients who may be unsuitable for surgery or have limited response to oral nonsteroidal anti-inflammatory drugs.
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Affiliation(s)
- Hiroakira Terakawa
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yuya Kawarai
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Ikuko Tajiri
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Kazuhide Inage
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Miyako Suzuki-Narita
- Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Jun Takeuchi
- Medical Affairs, Seikagaku Corporation, Tokyo, Japan
| | - Rui Hirasawa
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shigeo Hagiwara
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Junichi Nakamura
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Seiji Ohtori
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
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Yan X, Ye Y, Wang L, Xue J, Shen N, Li T. Platelet-rich plasma alleviates neuropathic pain in osteoarthritis by downregulating microglial activation. BMC Musculoskelet Disord 2024; 25:331. [PMID: 38725009 PMCID: PMC11080143 DOI: 10.1186/s12891-024-07437-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 04/12/2024] [Indexed: 05/13/2024] Open
Abstract
BACKGROUND The development of neuropathic pain (NP) is one of the reasons why the pain is difficult to treat, and microglial activation plays an important role in NP. Recently, platelet-rich plasma (PRP) has emerged as a novel therapeutic method for knee osteoarthritis (KOA). However, it's unclarified whether PRP has analgesic effects on NP induced by KOA and the underlying mechanisms unknown. PURPOSE To observe the analgesic effects of PRP on NP induced by KOA and explore the potential mechanisms of PRP in alleviating NP. METHODS KOA was induced in male rats with intra-articular injections of monosodium iodoacetate (MIA) on day 0. The rats received PRP or NS (normal saline) treatment at days 15, 17, and 19 after modeling. The Von Frey and Hargreaves tests were applied to assess the pain-related behaviors at different time points. After euthanizing the rats with deep anesthesia at days 28 and 42, the corresponding tissues were taken for subsequent experiments. The expression of activating transcription factor 3 (ATF3) in dorsal root ganglia (DRG) and ionized-calcium-binding adapter molecule-1(Iba-1) in the spinal dorsal horn (SDH) was detected by immunohistochemical staining. In addition, the knee histological assessment was performed by hematoxylin-eosin (HE) staining. RESULTS The results indicated that injection of MIA induced mechanical allodynia and thermal hyperalgesia, which could be reversed by PRP treatment. PRP downregulated the expression of ATF3 within the DRG and Iba-1 within the SDH. Furthermore, an inhibitory effect on cartilage degeneration was observed in the MIA + PRP group only on day 28. CONCLUSION These results indicate that PRP intra-articular injection therapy may be a potential therapeutic agent for relieving NP induced by KOA. This effect could be attributed to downregulation of microglial activation and reduction in nerve injury.
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Affiliation(s)
- Xiao Yan
- Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People's Republic of China
| | - Yinshuang Ye
- Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People's Republic of China
| | - Lin Wang
- Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People's Republic of China
| | - Junqiang Xue
- Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People's Republic of China
| | - Nana Shen
- Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People's Republic of China
| | - Tieshan Li
- Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People's Republic of China.
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Zhang Y, Li G, Wang J, Zhou F, Ren X, Su J. Small Joint Organoids 3D Bioprinting: Construction Strategy and Application. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2302506. [PMID: 37814373 DOI: 10.1002/smll.202302506] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Revised: 09/28/2023] [Indexed: 10/11/2023]
Abstract
Osteoarthritis (OA) is a chronic disease that causes pain and disability in adults, affecting ≈300 million people worldwide. It is caused by damage to cartilage, including cellular inflammation and destruction of the extracellular matrix (ECM), leading to limited self-repairing ability due to the lack of blood vessels and nerves in the cartilage tissue. Organoid technology has emerged as a promising approach for cartilage repair, but constructing joint organoids with their complex structures and special mechanisms is still challenging. To overcome these boundaries, 3D bioprinting technology allows for the precise design of physiologically relevant joint organoids, including shape, structure, mechanical properties, cellular arrangement, and biological cues to mimic natural joint tissue. In this review, the authors will introduce the biological structure of joint tissues, summarize key procedures in 3D bioprinting for cartilage repair, and propose strategies for constructing joint organoids using 3D bioprinting. The authors also discuss the challenges of using joint organoids' approaches and perspectives on their future applications, opening opportunities to model joint tissues and response to joint disease treatment.
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Affiliation(s)
- Yuan Zhang
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- Musculoskeletal Organoid Research Center, Shanghai University, Shanghai, 200444, China
- School of Medicine, Shanghai University, Shanghai, 200444, China
| | - Guangfeng Li
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- Musculoskeletal Organoid Research Center, Shanghai University, Shanghai, 200444, China
- School of Medicine, Shanghai University, Shanghai, 200444, China
- Department of Trauma Orthopedics, Zhongye Hospital, Shanghai, 200941, China
| | - Jian Wang
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- Musculoskeletal Organoid Research Center, Shanghai University, Shanghai, 200444, China
- School of Medicine, Shanghai University, Shanghai, 200444, China
| | - Fengjin Zhou
- Honghui Hospital, Xi'an Jiao Tong University, Xi'an, 710000, China
| | - Xiaoxiang Ren
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- Musculoskeletal Organoid Research Center, Shanghai University, Shanghai, 200444, China
| | - Jiacan Su
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- Musculoskeletal Organoid Research Center, Shanghai University, Shanghai, 200444, China
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Hossain MA, Alam MJ, Kim B, Kang CW, Kim JH. Ginsenoside-Rb1 prevents bone cartilage destruction through down-regulation of p-Akt, p-P38, and p-P65 signaling in rabbit. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 100:154039. [PMID: 35344713 DOI: 10.1016/j.phymed.2022.154039] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 02/08/2022] [Accepted: 03/09/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Osteoarthritis (OA) is the most common joint complaint resulting in pain, disability, and loss of quality of life. On the other hand, ginsenoside-Rb1 is a plant product derived from ginseng that possesses immune-regulation and anti-inflammatory activities. However, it has been reported that different rout of administration but hydrogel-based Ginsenoside-Rb1 in an OA rabbit model has not been investigated. PURPOSE The aim of this study was to investigate the potential effects of ginsenoside-Rb1 such as anti-arthritic activity in a rabbit knee OA model via NF- κB, PI3K/Akt, and P38/(MAPK) pathways. STUDY DESIGN In the current study, rabbit osteoarthritis was induced by hollow trephine on the femur trochlea and the hydrogel-based Ginsenoside-Rb1 sheets were inserted on the rabbit knee to assess the anti-arthritis activity of ginsenoside-Rb1 which is sustained release. METHODS After the hydrogel-based Rb1 sheet insert on the rabbit knee, macroscopic and micro CT was performed for investigation of chondroprotective effect. Matrix metalloproteinases (MMPs) and apoptotic expression were assessed through Immunohistochemistry and RT-PCR assay. In addition, the flow cytometry technique was used for the investigation of intracellular reactive oxygen species (ROS) production and histological changes were examined by HE, safranin O, and Masson trichrome staining method. Furthermore, the NF- κB, PI3K/Akt, and P38/(MAPK) pathways were investigated using Western blot analysis. RESULTS Macroscopic and micro CT investigation of hydrogel-Rb1 treatment showed a dose-dependent chondroprotective effect. Immunohistochemistry and RT-PCR revealed that expression of matrix metalloproteinases (MMPs) and apoptotic markers TNF-α, caspase-3, and bax are down-regulated in a dose-dependent fashion following implantation of hydrogel-Rb. Higher levels of intracellular reactive oxygen species (ROS) were observed in the OA group. In histopathological investigation of hydrogel-Rb1 exhibited larger amounts of chondro cells, glycosaminoglycan's, and collagen compared to the defect group. Furthermore, the NF- κB, PI3K/Akt, and P38/(MAPK) pathways were downregulated by hydrogel-Rb1 while the disease model showed upstream. In the meantime, MMP expression level was considerably down-regulated. CONCLUSIONS Our results indicate the protective effect of ginsenoside-Rb1 against OA pathogenesis through prevention of apoptosis with suppression of ROS production and activation of NF-κB signaling through downregulation of the MAPK and PI3K/Akt signaling pathways.
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Affiliation(s)
- Mohammad Amjad Hossain
- College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, 54596 79 Gobong-ro, Iksan-city, Jeollabuk-Do, Republic of Korea.
| | - Md Jahangir Alam
- College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, 54596 79 Gobong-ro, Iksan-city, Jeollabuk-Do, Republic of Korea
| | - Bumseok Kim
- College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, 54596 79 Gobong-ro, Iksan-city, Jeollabuk-Do, Republic of Korea
| | - Chang-Won Kang
- College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, 54596 79 Gobong-ro, Iksan-city, Jeollabuk-Do, Republic of Korea
| | - Jong-Hoon Kim
- College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, 54596 79 Gobong-ro, Iksan-city, Jeollabuk-Do, Republic of Korea.
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Yeater T, Zubcevic J, Allen K. Measures of cardiovascular function suggest autonomic nervous system dysregulation after surgical induction of joint injury in the male Lewis rat. Osteoarthritis Cartilage 2022; 30:586-595. [PMID: 35017058 PMCID: PMC9255271 DOI: 10.1016/j.joca.2021.12.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 11/01/2021] [Accepted: 12/02/2021] [Indexed: 02/02/2023]
Abstract
OBJECTIVES Functional changes in the autonomic nervous system may help explain variability in the progression of knee osteoarthritis (OA). Thus, the objective of this study was to evaluate autonomic nervous system shifts, measured via heart rate response variables, in rat knee joint injury and OA models. METHODS Cardiovascular characteristics were measured at baseline and bi-weekly for 8 weeks after skin incision, medial collateral ligament transection (MCLT), or MCLT+medial meniscus transection (MCLT+MMT). Heart rate was also assessed during a mild stressor (elevated maze). At endpoint, cardiovascular responses to mechanical knee stimuli were evaluated, as well as responses to 1-phenylbiguanide, a 5HT3A receptor agonist with reported ability to stimulate vagal responses. RESULTS During low activity, a slower heart rate occurred in MCLT (299 ± 10 bpm) and MCLT+MMT (310 ± 10 bpm) animals compared to controls (325 ± 10 bpm). Furthermore, patellar ligament mechanical stimuli produced an immediate decrease in heart rate and blood pressure in all groups. Finally, a larger drop in heart rate was observed in MCLT (252 ± 40 bpm) and MCLT+MMT (263 ± 49 bpm) following administration of 1-phenylbiguanide compared to skin incision (168 ± 45 bpm). CONCLUSIONS Acute mechanical stimulation of the patellar ligament produced drops in heart rate, suggesting a possible joint-brain connection that modulates autonomic responses. With both joint injury, cardiac vagal activation was altered in response to pharmacological stimulation, with chronic longitudinal heart rate reduction. These data provide some preliminary evidence of potential functional shifts in autonomic nervous system function in models of joint injury and OA.
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Affiliation(s)
- T.D. Yeater
- J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA
| | - J. Zubcevic
- Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA
| | - K.D. Allen
- J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA,Department of Orthopedic Surgery and Sports Medicine, College of Medicine, University of Florida, Gainesville, FL, USA,Address correspondence and reprint requests to: K.D. Allen, J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, 1275 Center Drive, Biomedical Sciences Building, Gainesville, FL, 32610, USA. Tel: (352)-273-9337. , (K.D. Allen)
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Stepien KM, Bentley A, Chen C, Dhemech MW, Gee E, Orton P, Pringle C, Rajan J, Saxena A, Tol G, Gadepalli C. Non-cardiac Manifestations in Adult Patients With Mucopolysaccharidosis. Front Cardiovasc Med 2022; 9:839391. [PMID: 35321113 PMCID: PMC8935042 DOI: 10.3389/fcvm.2022.839391] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 02/10/2022] [Indexed: 12/12/2022] Open
Abstract
Mucopolysaccharidoses (MPS) are a heterogeneous group of disorders that results in the absence or deficiency of lysosomal enzymes, leading to an inappropriate storage of glycosaminoglycans (GAGs) in various tissues of the body such as bones, cartilage, heart valves, arteries, upper airways, cornea, teeth, liver and nervous system. Clinical manifestations can become progressively exacerbated with age and affect their quality of life. Developments in advanced supportive treatment options such as enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT) may have improved patients' life span. Adult MPS patients require specialist clinical surveillance long-term. In many cases, in addition to the MPS-related health problems, they may develop age-related complications. Considering the complexity of their clinical manifestations and lack of guidelines on the management of adult MPS disorders, multispecialty and multidisciplinary teams' care is essential to diagnose and treat health problems that are likely to be encountered. This review presents non-cardiac clinical manifestations, their pathophysiology, management and long-term outcomes in adult MPS patients.
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Affiliation(s)
- Karolina M. Stepien
- Adult Inherited Metabolic Diseases, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom
| | - Andrew Bentley
- Northwest Ventilation Unit and Sleep Department, Wythenshawe Hospital, Manchester University National Health Service Foundation Trust, Manchester, United Kingdom
- Academic Health Sciences Centre, University of Manchester, Manchester, United Kingdom
- Intensive Care & Respiratory Medicine, Manchester University National Health Service Foundation Trust, Manchester, United Kingdom
| | - Cliff Chen
- Clinical Neuropsychology, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom
| | - M. Wahab Dhemech
- Northwest Ventilation Unit and Sleep Department, Wythenshawe Hospital, Manchester University National Health Service Foundation Trust, Manchester, United Kingdom
| | - Edward Gee
- Trauma and Orthopaedic Surgery, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom
| | - Peter Orton
- Trauma and Orthopaedic Surgery, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom
| | - Catherine Pringle
- Neurosurgery, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom
| | - Jonathan Rajan
- Manchester and Salford Pain Centre, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom
| | - Ankur Saxena
- Neurosurgery, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom
| | - Govind Tol
- Anaesthetics Department, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom
| | - Chaitanya Gadepalli
- Ear, Nose and Throat, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom
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Maqbool M, Fekadu G, Jiang X, Bekele F, Tolossa T, Turi E, Fetensa G, Fanta K. An up to date on clinical prospects and management of osteoarthritis. Ann Med Surg (Lond) 2021; 72:103077. [PMID: 34868573 PMCID: PMC8626656 DOI: 10.1016/j.amsu.2021.103077] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Revised: 11/14/2021] [Accepted: 11/16/2021] [Indexed: 12/19/2022] Open
Abstract
The rising prevalence of osteoarthritis (OA) in the general population has necessitated the development of novel treatment options. It is critical to recognize the joint as a separate entity participating in degenerative processes, as well as the multifaceted nature of OA. OA is incurable because there is currently no medication that can stop or reverse cartilage or bone loss. As this point of view has attracted attention, more research is being directed toward determining how the various joint components are impacted and how they contribute to OA pathogenesis. Over the next few years, several prospective therapies focusing on inflammation, cartilage metabolism, subchondral bone remodelling, cellular senescence, and the peripheral nociceptive pathway are predicted to transform the OA therapy landscape. Stem cell therapies and the use of various biomaterials to target articular cartilage (AC) and osteochondral tissues are now being investigated in considerable detail. Currently, laboratory-made cartilage tissues are on the verge of being used in clinical settings. This review focuses on the update of clinical prospects and management of osteoarthritis, as well as future possibilities for the treatment of OA.
Osteoarthritis (OA) is a general term that incorporates several different joint diseases. The exact pathophysiology of OA remains unclear. OA is incurable because there is currently no medication that can stop or reverse cartilage or bone loss. Nonsteroidal anti-inflammatory drugs are the most frequently prescribed medications to alleviate arthritic discomfort. Stem cell therapies to target articular cartilage and osteochondral tissues are now under investigation.
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Affiliation(s)
- Mudasir Maqbool
- Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar, 190006, Jammu and Kashmir, India
| | - Ginenus Fekadu
- School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T, Hong Kong.,School of Pharmacy, Institute of Health Sciences, Wollega University, Nekemte, Ethiopia
| | - Xinchan Jiang
- School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T, Hong Kong
| | - Firomsa Bekele
- Department of Pharmacy, College of Health Science, Mettu University, Mettu, Ethiopia
| | - Tadesse Tolossa
- Department of Public Health, Institute of Health Sciences, Wollega University, Nekemte, Ethiopia
| | - Ebisa Turi
- Department of Public Health, Institute of Health Sciences, Wollega University, Nekemte, Ethiopia
| | - Getahun Fetensa
- School of Nursing and Midwifery, Institute of Health Sciences, Wollega University, Nekemte, Ethiopia
| | - Korinan Fanta
- School of Pharmacy, Institute of Health Science, Jimma University, Jimma, Ethiopia
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Arthroscopic Arthroplasty for Knee Osteoarthritis: Denervation of Subchondral Bone and Comprehensive Synovectomy. Arthrosc Tech 2021; 10:e2651-e2657. [PMID: 35004145 PMCID: PMC8719106 DOI: 10.1016/j.eats.2021.08.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Accepted: 08/05/2021] [Indexed: 02/03/2023] Open
Abstract
Knee osteoarthritis is the most common orthopaedic disorder, and surgical treatments are always inevitable. Among the various surgical options, arthroscopic treatment is not favorable because strong evidence supporting its application is scarce. However, we consider that the unsatisfactory clinical results of arthroscopic surgery occur because the pain-relieving mechanism of joint replacement is not realized in the too simple and not well-designed arthroscopic procedures. Thus, we use a set of arthroscopic procedures to realize the pain-relieving mechanism of joint replacement, which we call "arthroscopic arthroplasty." The most important parts of this technique are denervation of the subchondral bone and comprehensive synovectomy. Our clinical results indicate that we can obtain even better functional improvement with this technique than that with joint replacement. We consider that the introduction of this technique will arouse interest in the development of arthroscopic surgical procedures for knee osteoarthritis.
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Kwok CHT, Kohro Y, Mousseau M, O'Brien MS, Matyas JR, McDougall JJ, Trang T. Role of Primary Afferents in Arthritis Induced Spinal Microglial Reactivity. Front Immunol 2021; 12:626884. [PMID: 33897685 PMCID: PMC8058457 DOI: 10.3389/fimmu.2021.626884] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Accepted: 03/18/2021] [Indexed: 11/18/2022] Open
Abstract
Increased afferent input resulting from painful injury augments the activity of central nociceptive circuits via both neuron-neuron and neuron-glia interactions. Microglia, resident immune cells of the central nervous system (CNS), play a crucial role in the pathogenesis of chronic pain. This study provides a framework for understanding how peripheral joint injury signals the CNS to engage spinal microglial responses. During the first week of monosodium iodoacetate (MIA)-induced knee joint injury in male rats, inflammatory and neuropathic pain were characterized by increased firing of peripheral joint afferents. This increased peripheral afferent activity was accompanied by increased Iba1 immunoreactivity within the spinal dorsal horn indicating microglial activation. Pharmacological silencing of C and A afferents with co-injections of QX-314 and bupivacaine, capsaicin, or flagellin prevented the development of mechanical allodynia and spinal microglial activity after MIA injection. Elevated levels of ATP in the cerebrospinal fluid (CSF) and increased expression of the ATP transporter vesicular nucleotide transporter (VNUT) in the ipsilateral spinal dorsal horn were also observed after MIA injections. Selective silencing of primary joint afferents subsequently inhibited ATP release into the CSF. Furthermore, increased spinal microglial reactivity, and alleviation of MIA-induced arthralgia with co-administration of QX-314 with bupivacaine were recapitulated in female rats. Our results demonstrate that early peripheral joint injury activates joint nociceptors, which triggers a central spinal microglial response. Elevation of ATP in the CSF, and spinal expression of VNUT suggest ATP signaling may modulate communication between sensory neurons and spinal microglia at 2 weeks of joint degeneration.
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Affiliation(s)
- Charlie H T Kwok
- Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB, Canada.,Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
| | - Yuta Kohro
- Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB, Canada.,Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.,Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
| | - Michael Mousseau
- Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB, Canada.,Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
| | - Melissa S O'Brien
- Departments of Pharmacology and Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, NS, Canada
| | - John R Matyas
- Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB, Canada
| | - Jason J McDougall
- Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
| | - Tuan Trang
- Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB, Canada.,Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
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10
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Wu JQ, Jiang N, Yu B. Mechanisms of action of neuropeptide Y on stem cells and its potential applications in orthopaedic disorders. World J Stem Cells 2020; 12:986-1000. [PMID: 33033559 PMCID: PMC7524693 DOI: 10.4252/wjsc.v12.i9.986] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 05/25/2020] [Accepted: 06/02/2020] [Indexed: 02/06/2023] Open
Abstract
Musculoskeletal disorders are the leading causes of disability and result in reduced quality of life. The neuro-osteogenic network is one of the most promising fields in orthopaedic research. Neuropeptide Y (NPY) system has been reported to be involved in the regulations of bone metabolism and homeostasis, which also provide feedback to the central NPY system via NPY receptors. Currently, potential roles of peripheral NPY in bone metabolism remain unclear. Growing evidence suggests that NPY can regulate biological actions of bone marrow mesenchymal stem cells, hematopoietic stem cells, endothelial cells, and chondrocytes via a local autocrine or paracrine manner by different NPY receptors. The regulative activities of NPY may be achieved through the plasticity of NPY receptors, and interactions among the targeted cells as well. In general, NPY can influence proliferation, apoptosis, differentiation, migration, mobilization, and cytokine secretion of different types of cells, and play crucial roles in the development of bone delayed/non-union, osteoporosis, and osteoarthritis. Further basic research should clarify detailed mechanisms of action of NPY on stem cells, and clinical investigations are also necessary to comprehensively evaluate potential applications of NPY and its receptor-targeted drugs in management of musculoskeletal disorders.
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Affiliation(s)
- Jian-Qun Wu
- Department of Orthopedics and Traumatology, Huadu District People’s Hospital, Guangzhou 510800, Guangdong Province, China
| | - Nan Jiang
- Division of Orthopaedics and Traumatology, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Bin Yu
- Division of Orthopaedics and Traumatology, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
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Muschter D, Fleischhauer L, Taheri S, Schilling AF, Clausen-Schaumann H, Grässel S. Sensory neuropeptides are required for bone and cartilage homeostasis in a murine destabilization-induced osteoarthritis model. Bone 2020; 133:115181. [PMID: 31926346 DOI: 10.1016/j.bone.2019.115181] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 11/13/2019] [Accepted: 11/28/2019] [Indexed: 12/16/2022]
Abstract
Numerous studies identified a role for the sensory neuropeptides substance P (SP) and alpha calcitonin gene-related peptide (αCGRP) in osteoarthritis (OA) pain behavior. Surprisingly, little attention has been paid on how their trophic effects on cartilage and bone cells might affect structural changes of bone and cartilage in OA pathology. Here, we sought to elucidate sensory neuropeptides influence on structural alterations of bone and cartilage during murine OA pathophysiology. OA was induced by destabilization of the medial meniscus (DMM) in the right knee joint of 12 weeks old male C57Bl/6J wildtype (WT) mice and mice either deficient for SP (tachykinin 1 (Tac1)-/-) or αCGRP. By OARSI histopathological grading we observed significant cartilage matrix degradation after DMM surgery in αCGRP-deficient mice after 4 weeks whereas Tac1-/- scores were not different to sham mice before 12 weeks after surgery. Indentation-type atomic force microscopy (IT-AFM) identified a strong superficial zone (SZ) cartilage phenotype in Tac1-/- Sham mice. Opposed to WT and αCGRP-/- mice, SZ cartilage of Tac1-/- mice softened 2 weeks after OA induction. In Tac1-/- DMM mice, bone volume to total volume ratio (BV/TV) increased significantly compared to the Tac1-/- Sham group, 2 weeks after surgery. WT mice had reduced BV/TV compared to αCGRP-/- and Tac1-/- mice after 12 weeks. Increased calcified cartilage thickness and medial condyle diameter were detected in the medial tibia of all groups 8 weeks after OA induction by nanoCT analysis. Meniscal ossification occurred in all OA groups, but was significantly stronger in the absence of neuropeptides. Increased serum concentration of the respective non-deleted neuropeptide was observed in both neuropeptide-deficient mice strains. Both neuropeptides protect from age-related bone structural changes under physiological conditions and SP additionally demonstrates an anabolic effect on bone structure preservation in a pathophysiological situation. Both neuropeptide deficient mice display an intrinsic structural cartilage matrix phenotype that might alter progression of cartilage degeneration in OA.
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Affiliation(s)
- Dominique Muschter
- Dept. of Orthopaedic Surgery, Experimental Orthopaedics, Centre for Medical Biotechnology (ZMB), Bio Park 1, University of Regensburg, Germany.
| | - Lutz Fleischhauer
- Department of Applied Sciences and Mechatronics, University of Applied Sciences Munich, Germany; Laboratory of Experimental Surgery and Regenerative Medicine, Clinic for General, Trauma and Reconstructive Surgery, Ludwig-Maximilians-University, Munich, Germany; Center for NanoScience, Ludwig-Maximilians-University, Munich, Germany.
| | - Shahed Taheri
- Department of Trauma Surgery, Orthopedics and Plastic Surgery, University Medicine Göttingen.
| | - Arndt F Schilling
- Department of Trauma Surgery, Orthopedics and Plastic Surgery, University Medicine Göttingen.
| | - Hauke Clausen-Schaumann
- Department of Applied Sciences and Mechatronics, University of Applied Sciences Munich, Germany.
| | - Susanne Grässel
- Dept. of Orthopaedic Surgery, Experimental Orthopaedics, Centre for Medical Biotechnology (ZMB), Bio Park 1, University of Regensburg, Germany.
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Pastrana MJ, Zaidenberg EE, Palumbo D, Cesca FJ, Zaidenberg CR. Innervation of the Proximal Interphalangeal Joint: An Anatomical Study. J Hand Surg Am 2019; 44:422.e1-422.e5. [PMID: 30172449 DOI: 10.1016/j.jhsa.2018.07.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Revised: 05/16/2018] [Accepted: 07/17/2018] [Indexed: 02/02/2023]
Abstract
PURPOSE To describe the innervation of the proximal interphalangeal (PIP) joint of the fingers as well as the anatomical relations of the articular branches. METHODS In this anatomical study, 52 fresh-frozen index, long, ring, and little fingers of 6 male and 4 female cadavers were dissected after injection of a colored latex composite. The anatomical dissections were performed under ×3.5 and ×6.0 magnifications. The numbers of articular nerve branches that penetrated the PIP joint on both sides of the fingers were quantified and patterns of innervation were established. We also measured the origin of the branches regarding the PIP articular line, the angle of emergence, and the diameter of the nerves. RESULTS The PIP joint was innervated by one articular branch of the proper palmar digital nerve at each side of the finger (pattern 1). Less frequently, an additional distal branch from the same proper palmar digital nerve was found (pattern 2). Dorsal articular branches were identified innervating only the little finger. CONCLUSIONS The findings suggest that PIP joints of the fingers have a consistent articular nerve anatomy predominantly provided at the palmar aspect of the joint. These findings provide an anatomical basis for procedures to denervate the PIP joint. CLINICAL RELEVANCE An accurate understanding of peripheral nerve anatomy of the PIP joint is essential to improve outcomes in denervation techniques.
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Affiliation(s)
- Martin Jose Pastrana
- Department of Anatomy, School of Medicine, University of Buenos Aires, Salta, Argentina
| | - Ezequiel Ernesto Zaidenberg
- Department of Anatomy, School of Medicine, University of Buenos Aires, Salta, Argentina; Department of Orthopaedics, Italian Hospital of Buenos Aires, Salta, Argentina; Kleinert-Kutz Institute for Hand and Microsurgery, Louisville, KY
| | - Dante Palumbo
- Kleinert-Kutz Institute for Hand and Microsurgery, Louisville, KY
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Gatenholm B, Brittberg M. Neuropeptides: important regulators of joint homeostasis. Knee Surg Sports Traumatol Arthrosc 2019; 27:942-949. [PMID: 30039292 DOI: 10.1007/s00167-018-5074-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Accepted: 07/17/2018] [Indexed: 12/31/2022]
Abstract
PURPOSE This review explores the mechanisms of joint pain with a special focus on the role of neuropeptides in pain transmission and their potential role in the progression of joint degeneration as seen in osteoarthritis. METHODS A literature search was performed on papers published between January 1990 and September 2017 using the Web of Science Core Collection, MEDLINE and Scopus databases. RESULTS What is seen in the subchondral bone and synovia is mirrored in the central nervous system (CNS). Substance P, calcitonin gene-related peptide, vasoactive intestinal peptide and neuropeptide Y are the major peptides involved both in the generation of pain as well as reducing pain post-joint trauma. The interplay between them and other neuropeptides and cytokines influence how noxious stimuli are transduced, transmitted and modulated for a final pain perception as part of a complex cascade of events. There is a close interaction between the different components in the joint that together cross-talk to adapt to load and catabolic factors during injury and inflammation. CONCLUSION The articular joint should be seen as an organ where local joint pain development and maintenance is influenced by interplay between the local transmitters in the joints as well as their dependence on the CNS. A slow-release cocktail of mixed antibodies targeted against neuropeptides and receptor blockers/stimulators involved in the events of early joint pain or any inflammatory joint disease is a future treatment target. LEVEL OF EVIDENCE V.
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Affiliation(s)
- Birgitta Gatenholm
- Department of Orthopaedics, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. .,Sahlgrenska University Hospital, Mölndal, Sweden.
| | - Mats Brittberg
- Department of Orthopaedics, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.,Hallands Sjukhus, Kungsbacka, Sweden
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Pain in Mucopolysaccharidoses: Analysis of the Problem and Possible Treatments. Int J Mol Sci 2018; 19:ijms19103063. [PMID: 30297617 PMCID: PMC6213542 DOI: 10.3390/ijms19103063] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2018] [Revised: 09/30/2018] [Accepted: 10/02/2018] [Indexed: 01/01/2023] Open
Abstract
Mucopolysaccharidosis (MPS) are a group of lysosomal storage disorders that are caused by the deficiency of enzymes involving in the catabolism of glycosaminoglycan (GAGs). GAGs incompletely degraded accumulate in many sites, damaging tissues and cells, leading to a variety of clinical manifestations. Many of these manifestations are painful, but few data are available in the literature concerning the prevalence, etiology, and pathogenesis of pain in children with MPS. This review, through the analysis of the data available the in literature, underscores the relevant prevalence of pain in MPSs’ children, provides the instruments to discern the etiopathogenesis of the disease and of pain, illustrates the available molecules for the management of pain and the possible advantages of non-pharmacological pain therapy in MPSs’ patients.
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Abstract
OBJECTIVE Topical delivery of drugs is an alternative to oral administration, often with similar efficacy but potentially a more favorable tolerability profile. However, topical formulations need to be able to penetrate the skin and permeate to the target areas in quantities sufficient to exert a therapeutic effect. Many factors can affect this process, including the physicochemical properties of the drug, the formulation used, and the site and mode of application. It is believed that measurement of drug concentrations at the sites of action may be an indicator of their likely efficacy. This review addresses these issues, with reference to topically administered diclofenac in osteoarthritis. METHODS Articles relevant to this review were identified after a systematic search of Medline and Embase, using the key words "diclofenac", "topical administration" and "osteoarthritis" in the search strategy. RESULTS The sparse data available indicate that topical diclofenac can penetrate and permeate to deeper tissues, with a lower plasma to tissue ratio than oral diclofenac. The tissue diclofenac levels after topical delivery are sustained over time (at least several hours). However, there is not enough data to establish how diclofenac levels in the joint compare with IC50 levels (50% of the maximum inhibition of prostaglandin synthesis) established following oral administration. CONCLUSIONS After topical application, diclofenac can penetrate the skin and permeate to deeper tissues, where it reaches a concentration that appears to be sufficient to exert a therapeutic effect. More robust methods are required for in vivo characterization to better estimate the clinical efficacy of topically applied drugs.
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Affiliation(s)
- Martina Hagen
- a GlaxoSmithKline Consumer Healthcare , Nyon , Switzerland
| | - Mark Baker
- a GlaxoSmithKline Consumer Healthcare , Nyon , Switzerland
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Si HB, Yang TM, Zeng Y, Zhou ZK, Pei FX, Lu YR, Cheng JQ, Shen B. Correlations between inflammatory cytokines, muscle damage markers and acute postoperative pain following primary total knee arthroplasty. BMC Musculoskelet Disord 2017. [PMID: 28623906 PMCID: PMC5473999 DOI: 10.1186/s12891-017-1597-y] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Despite the success of total knee arthroplasty (TKA) in reducing knee pain and improving functional disability, the management of acute postoperative pain is still unsatisfactory. This study was aimed to quantitatively analyze the possible correlations between inflammatory cytokines, muscle damage markers and acute postoperative pain following primary TKA. METHODS Patients scheduled for unilateral primary TKA were consecutively included, the serial changes of the numerical rating scale (NRS) at rest (NRSR) and at walking (NRSW), serum inflammatory cytokines and muscle damage markers were assessed before surgery (T0) and at postoperative day 1, 2, 3 and 5 (T1-T4, respectively); while pain disability questionnaire (PDQ) and synovial fluid inflammatory cytokines were evaluated at T0. The correlations between inflammatory cytokines, muscle damage markers and pain scores were examined, and Bonferroni correction was applied for multiple comparisons. RESULTS Ninety six patients were included for serum markers and pain evaluations at T0-T4, while 54 (56.25%) for synovial fluid cytokines at T0. The NRSR at T1 and T2 were positively correlated with preoperative NRSW, while the NRSW at T1 to T4 were positively correlated with preoperative NRSR, NRSW and PDQ (all p < 0.05). The NRSR was positively correlated with serum PGE2, IL-6, and CK at T1; the NRSW was positively correlated with serum CRP at T1, with PGE2 and IL-6 at T1 to T3, with CK at T2 and T4, and with Mb and LDH at T1 to T4 (all p < 0.003). Meanwhile, positive correlations were observed between preoperative NRSW and synovial fluid PGE2, IL-6, IL-8, or TNF-α, as well as between PDQ and PGE2 (all p < 0.003), but no associations between postoperative pain scores and preoperative synovial fluid cytokines was found (all p ≥ 0.003). Additionally, the NRSR at T1 and T2, and NRSW at T1 to T4 were positively correlated with body mass index (all p < 0.05). CONCLUSIONS Serum inflammatory cytokines and muscle damage markers are positively correlated with acute postoperative pain following primary TKA, and the key cytokines (CRP, PGE2, and IL-6) and markers (Mb, CK and LDH) may serve as the targets for developing novel analgesic strategies.
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Affiliation(s)
- Hai-Bo Si
- Department of Orthopedic Surgery, West China Hospital, Sichuan University, 37th Guoxue Road, Chengdu, Sichuan, 610041, China.,Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, No.1 Keyuan 4th Road, Chengdu, Sichuan, 610041, China
| | - Ti-Min Yang
- Department of Orthopedic Surgery, West China Hospital, Sichuan University, 37th Guoxue Road, Chengdu, Sichuan, 610041, China
| | - Yi Zeng
- Department of Orthopedic Surgery, West China Hospital, Sichuan University, 37th Guoxue Road, Chengdu, Sichuan, 610041, China
| | - Zong-Ke Zhou
- Department of Orthopedic Surgery, West China Hospital, Sichuan University, 37th Guoxue Road, Chengdu, Sichuan, 610041, China
| | - Fu-Xing Pei
- Department of Orthopedic Surgery, West China Hospital, Sichuan University, 37th Guoxue Road, Chengdu, Sichuan, 610041, China
| | - Yan-Rong Lu
- Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, No.1 Keyuan 4th Road, Chengdu, Sichuan, 610041, China
| | - Jing-Qiu Cheng
- Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, No.1 Keyuan 4th Road, Chengdu, Sichuan, 610041, China.
| | - Bin Shen
- Department of Orthopedic Surgery, West China Hospital, Sichuan University, 37th Guoxue Road, Chengdu, Sichuan, 610041, China.
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Nemery E, Gabriel A, Piret J, Antoine N. Nociceptive and sympathetic innervations in the abaxial part of the cranial horn of the equine medial meniscus: an immunohistochemical approach. J Anat 2016; 229:791-799. [PMID: 27345299 DOI: 10.1111/joa.12517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/02/2016] [Indexed: 11/28/2022] Open
Abstract
In athletic horses, diseases leading to lameness are of great importance due to the loss of performance and the resultant economic concerns. Although stifle lesions are frequent in the hindlimb, due to the large size and complexity of the joint, and although meniscal tears have been identified as the most common soft tissue injuries in this joint, little is known about the mechanism that causes the painful sensation and thus the lameness. The aim of our study was to highlight any peripheral fibres involved in meniscal nociception in five macroscopically sound cranial horns of the equine medial meniscus, which has been one of the most common sites reported for equine meniscal injuries. Immunohistochemical stainings were performed using antibodies against Substance P in order to identify nociceptive fibres; against tyrosine hydroxylase for detecting postganglionic sympathetic fibres; and against glial fibrillary acidic proteins in order to identify Schwann cells. Our work highlights for the first time the presence of nociceptive and sympathetic fibres in equine menisci. They were found in the abaxial part of the cranial horn of the equine medial meniscus. This study suggests that when the abaxial part is injured, the meniscus itself could be the source of pain. These findings could provide a better understanding of the clinical presentation of horses with meniscal injury and contribute towards improving therapeutic strategies to alleviate pain in cases of equine meniscal injury.
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Affiliation(s)
- Elodie Nemery
- Anatomy Unit, Department of Morphology and Pathology, FARAH Research Center, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium
| | - Annick Gabriel
- Anatomy Unit, Department of Morphology and Pathology, FARAH Research Center, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium
| | - Joëlle Piret
- Histology Unit, Department of Morphology and Pathology, FARAH Research Center, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium
| | - Nadine Antoine
- Histology Unit, Department of Morphology and Pathology, FARAH Research Center, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium
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Paul J, Barg A, Kretzschmar M, Pagenstert G, Studler U, Hügle T, Wegner NJ, Valderrabano V, Geurts J. Increased Osseous (99m)Tc-DPD Uptake in End-Stage Ankle Osteoarthritis: Correlation Between SPECT-CT Imaging and Histologic Findings. Foot Ankle Int 2015; 36:1438-47. [PMID: 26231199 DOI: 10.1177/1071100715596745] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND We analyzed the histopathologic findings in end-stage osteoarthritic ankle joint tissue that display increased uptake of bone-seeking radiotracer in single-photon emission computed tomography-computed tomography (SPECT-CT) imaging. METHODS Six consecutive patients with end-stage osteoarthritis undergoing total ankle replacement received preoperative SPECT-CT imaging using (99m)Technetium dicarboxypropane diphosphonate ((99m)Tc-DPD). Using imaging data for stratification, osteochondral tissue sections were prepared from SPECT-positive (+) and -negative (-) areas of tibial and talar resection specimens. Histomorphometric analyses of osteoblast numbers, collagen deposition, and cartilage degeneration were performed on hematoxylin and eosin, van Gieson's and Safranin-O stained tissue sections. Osteoclast activity was visualized using tartrate-resistant acid phosphatase (TRAP) staining. RESULTS Increased (99m)Tc-DPD uptake was observed exclusively subjacent to the subchondral bone plate of tibial and talar joint compartments. SPECT(-) tissues displayed typical fatty marrow morphology containing mainly collagen-positive blood vessels and few marrow and bone-lining cells. SPECT(+) tissues were characterized by increased numbers of active bone-lining osteoblasts depositing collagen fibers. Collagen area fraction of subchondral bone marrow was significantly increased in SPECT(+) (0.52 ± 0.21) compared with SPECT(-) (0.29 ± 0.13) tissues (P = .30). Multinucleated TRAP(+) osteoclasts were absent from bone formation sites, but associated with vascular structures invading articular cartilage through the subchondral bone plate. Increased (99m)Tc-DPD uptake was specifically and strongly correlated with increased osteoblast numbers (P = .011), and with collagen area fraction (P = .030) but not with Mankin score (P = .202), or with osteoclast number (P = .576). CONCLUSION Subchondral bone tissues in SPECT(+) areas of end-stage ankle osteoarthritis were histologically characterized by increased osteoblast-mediated bone formation in the absence of functional osteoclasts, and increased cellularity and collagen deposition in marrow tissues. CLINICAL SIGNIFICANCE Our findings suggest a pathologic bone-remodeling process in end-stage ankle OA areas with increased (99m)Tc-DPD uptake.
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Affiliation(s)
- Jochen Paul
- Praxisklinik Rennbahn AG, Basel, Switzerland
| | | | | | | | - Ueli Studler
- University Hospital of Basel, Basel, Switzerland
| | - Thomas Hügle
- University Hospital of Basel, Basel, Switzerland
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Effects of acupuncture knife on inflammatory factors and pain in third lumbar vertebrae transverse process syndrome model rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2014; 2014:892406. [PMID: 25544854 PMCID: PMC4269310 DOI: 10.1155/2014/892406] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Accepted: 10/08/2014] [Indexed: 01/24/2023]
Abstract
The aim of this paper was to explore the long-term effects and pain relief mechanism of acupuncture knife on third lumbar vertebrae (L3) transverse process syndrome. Forty SD rats were randomized into control, model, electroacupuncture (EA), and acupuncture knife (AK) group. Except control rats, other rats were subjected to an operation to emulate L3 transverse process syndrome. Fourteen days after the operation, EA and AK rats were given electroacupuncture and acupuncture knife treatments, respectively. Fifty-six days after the operation, enzyme-linked immunosorbent assay was used to measure substance P (SP), 5-hydroxytryptamine (5-HT), interleukin-1β (IL-1β), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β) in peripheral blood. The tail flick test was used to observe pain threshold. We found that rats with the simulation operation had significantly higher levels of SP, 5-HT, IL-1, IL-10, TNF-α, and TGF-β, while the AK rats had lower levels. In addition, the pain threshold of AK rats was similar to that of control rats. AK pretreatment could alleviate pain through modulating inflammatory response.
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Kim K, Lam J, Lu S, Spicer PP, Lueckgen A, Tabata Y, Wong ME, Jansen JA, Mikos AG, Kasper FK. Osteochondral tissue regeneration using a bilayered composite hydrogel with modulating dual growth factor release kinetics in a rabbit model. J Control Release 2013; 168:166-78. [PMID: 23541928 DOI: 10.1016/j.jconrel.2013.03.013] [Citation(s) in RCA: 104] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2013] [Accepted: 03/20/2013] [Indexed: 12/11/2022]
Abstract
Biodegradable oligo(poly(ethylene glycol) fumarate) (OPF) composite hydrogels have been investigated for the delivery of growth factors (GFs) with the aid of gelatin microparticles (GMPs) and stem cell populations for osteochondral tissue regeneration. In this study, a bilayered OPF composite hydrogel that mimics the distinctive hierarchical structure of native osteochondral tissue was utilized to investigate the effect of transforming growth factor-β3 (TGF-β3) with varying release kinetics and/or insulin-like growth factor-1 (IGF-1) on osteochondral tissue regeneration in a rabbit full-thickness osteochondral defect model. The four groups investigated included (i) a blank control (no GFs), (ii) GMP-loaded IGF-1 alone, (iii) GMP-loaded IGF-1 and gel-loaded TGF-β3, and (iv) GMP-loaded IGF-1 and GMP-loaded TGF-β3 in OPF composite hydrogels. The results of an in vitro release study demonstrated that TGF-β3 release kinetics could be modulated by the GF incorporation method. At 12weeks post-implantation, the quality of tissue repair in both chondral and subchondral layers was analyzed based on quantitative histological scoring. All groups incorporating GFs resulted in a significant improvement in cartilage morphology compared to the control. Single delivery of IGF-1 showed higher scores in subchondral bone morphology as well as chondrocyte and glycosaminoglycan amount in adjacent cartilage tissue when compared to a dual delivery of IGF-1 and TGF-β3, independent of the TGF-β3 release kinetics. The results suggest that although the dual delivery of TGF-β3 and IGF-1 may not synergistically enhance the quality of engineered tissue, the delivery of IGF-1 alone from bilayered composite hydrogels positively affects osteochondral tissue repair and holds promise for osteochondral tissue engineering applications.
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Affiliation(s)
- Kyobum Kim
- Department of Bioengineering, Rice University, Houston, USA
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