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Cells Oct 2019The synovium exercises its main function in joint homeostasis through the secretion of factors (such as lubricin and hyaluronic acid) that are critical for the joint... (Review)
Review
The synovium exercises its main function in joint homeostasis through the secretion of factors (such as lubricin and hyaluronic acid) that are critical for the joint lubrication and function. The main synovium cell components are fibroblast-like synoviocytes, mesenchymal stromal/stem cells and macrophage-like synovial cells. In the synovium, cells of mesenchymal origin modulate local inflammation and fibrosis, and interact with different fibroblast subtypes and with resident macrophages. In pathologic conditions, such as rheumatoid arthritis, fibroblast-like synoviocytes proliferate abnormally, recruit mesenchymal stem cells from subchondral bone marrow, and influence immune cell activity through epigenetic and metabolic adaptations. The resulting synovial hyperplasia leads to secondary cartilage destruction, joint swelling, and pain. In the present review, we summarize recent findings on the molecular signature and the roles of stromal cells during synovial pannus formation and rheumatoid arthritis progression.
Topics: Arthritis, Rheumatoid; Fibroblasts; Humans; Inflammation; Mesenchymal Stem Cells; Stromal Cells; Synovial Membrane; Synoviocytes; Synovitis
PubMed: 31618926
DOI: 10.3390/cells8101257 -
Arthritis Research & Therapy Feb 2023Osteoarthritis (OA) is a chronic, progressive degenerative whole joint disease that affects the articular cartilage, subchondral bone, ligaments, capsule, and synovium.... (Review)
Review
Osteoarthritis (OA) is a chronic, progressive degenerative whole joint disease that affects the articular cartilage, subchondral bone, ligaments, capsule, and synovium. While it is still believed to be a mechanically driven disease, the role of underlying co-existing inflammatory processes and mediators in the onset of OA and its progression is now more appreciated. Post-traumatic osteoarthritis (PTOA) is a subtype of OA that occurs secondary to traumatic joint insults and is widely used in pre-clinical models to help understand OA in general. There is an urgent need to develop new treatments as the global burden is considerable and expanding. In this review, we focus on the recent pharmacological advances in the treatment of OA and summarize the most significant promising agents based on their molecular effects. Those are classified here into broad categories: anti-inflammatory, modulation of the activity of matrix metalloproteases, anabolic, and unconventional pleiotropic agents. We provide a comprehensive analysis of the pharmacological advances in each of these areas and highlight future insights and directions in the OA field.
Topics: Humans; Osteoarthritis; Cartilage, Articular; Bone and Bones; Synovial Membrane; Disease Management
PubMed: 36800974
DOI: 10.1186/s13075-023-03006-w -
FEBS Open Bio Nov 2020Joint contracture (also known as arthrofibrosis) is a fibrotic joint disorder characterized by excessive collagen production to form fibrotic scar tissue and adhesions...
Joint contracture (also known as arthrofibrosis) is a fibrotic joint disorder characterized by excessive collagen production to form fibrotic scar tissue and adhesions within joint capsules. This can severely affect day-to-day activities and quality of life because of a restricted range of motion in affected joints. The precise pathogenic mechanism underlying joint contractures is not fully understood. Lumican belongs to the class II small leucine-rich repeat proteoglycan superfamily, which makes up collagen fibrils in the extracellular matrix. Lumican is ubiquitously expressed in the skin, liver, heart, uterus and articular cartilage and has reported roles in cell migration, proliferation, angiogenesis and Toll-like receptor 4 signaling. Previous research has suggested that lumican is involved in the pathogenesis of several fibrotic diseases. Because joint contracture resembles a fibrotic disease, we aimed to investigate the role of lumican in the development of joint contracture in vitro. Here, we showed that protein levels were up-regulated in the fibrotic joint capsule versus control. We observed that lumican significantly enhanced the proliferation, migration and fibroblast-myofibroblast transition of synovial fibroblasts. Moreover, lumican led to increased transcription of alpha-smooth muscle actin, matrix metallopeptidase 9, Collagen I, plasminogen activator inhibitor 1 and transforming growth factor-β in vitro. Lumican treatment promoted collagen lattice contraction in a dose-dependent manner as early as 24 h after treatment. Thus, our studies reveal that lumican could promote fibroblast-myofibroblast transition and joint contracture.
Topics: Actins; Cell Movement; Cell Proliferation; Collagen; Female; Fibrosis; Humans; Joint Capsule; Joints; Lumican; Male; Matrix Metalloproteinase 9; Middle Aged; Myofibroblasts; Plasminogen Activator Inhibitor 1; RNA, Messenger; Signal Transduction; Synovial Membrane; Transforming Growth Factor beta; Up-Regulation
PubMed: 32910552
DOI: 10.1002/2211-5463.12974 -
Clinical and Experimental Rheumatology 2021Metformin is a known therapeutic agent for diabetes. Recently, several reports suggested the possibility of improvement in autoimmune disease and malignancy conditions...
OBJECTIVES
Metformin is a known therapeutic agent for diabetes. Recently, several reports suggested the possibility of improvement in autoimmune disease and malignancy conditions through the effect of metformin on the immune system. Although there have been reports on the therapeutic effects of metformin on mouse models of collagen-induced arthritis, simulating human rheumatoid arthritis (RA), the effect of metformin on human RA remains unknown. Therefore, we investigated the inhibitory effect of metformin on the pathogenesis of human RA in vitro.
METHODS
Osteoclastogenesis was evaluated with or without metformin. through tartrate-resistant acid phosphatase staining, osteoclast-specific enzyme expression analysis, and a bone resorption assay. Human fibroblast-like synoviocyte MH7A cells were stimulated with TNF-α, and the expression of proinflammatory cytokines and protease and growth factor genes was evaluated with or without metformin. Metformin has been used to evaluate their potential modulatory effects on cells treated with TNF-α. Moreover, we examined angiogenesis by performing a tube formation assay using human umbilical vein endothelial cells (HUVECs) with or without metformin.
RESULTS
Osteoclastogenesis was suppressed in the presence of metformin, and the expression of osteoclast-specific genes was reduced. The TNF-α-induced expression of inflammatory cytokines and protease and growth factor genes in MH7A cells was downregulated by metformin. Additionally, the induced formation of tubular networks in HUVECs was also disrupted following treatment with metformin.
CONCLUSIONS
These results suggest that metformin might improve the pathogenesis of RA, including joint inflammation and destruction. Thus, metformin might be utilised as a potential therapeutic agent in the treatment of RA.
Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Cells, Cultured; Endothelial Cells; Metformin; Osteoclasts; Synovial Membrane
PubMed: 32828146
DOI: 10.55563/clinexprheumatol/zn2u9h -
Seminars in Immunopathology Jun 2017The profound alterations in the structure, cellular composition, and function of synovial tissue in rheumatoid arthritis (RA) are the basis for the persistent... (Review)
Review
The profound alterations in the structure, cellular composition, and function of synovial tissue in rheumatoid arthritis (RA) are the basis for the persistent inflammation and cumulative joint destruction that are hallmarks of this disease. In RA, the synovium develops characteristics of a tertiary lymphoid organ, with extensive infiltration of lymphocytes and myeloid cells. Concurrently, the fibroblast-like synoviocytes undergo massive hyperplasia and acquire a tissue-invasive phenotype. In this review, we summarize key components of these processes, focusing on recently-described roles of selected molecular markers of these cellular components of RA synovitis.
Topics: Animals; Antirheumatic Agents; Arthritis, Rheumatoid; Biomarkers; Cell Communication; Gene Expression Regulation; Humans; Joint Capsule; Molecular Targeted Therapy; Signal Transduction; Synovial Membrane
PubMed: 28497350
DOI: 10.1007/s00281-017-0631-3 -
Matrix Biology : Journal of the... Oct 2014Limb synovial joints are intricate structures composed of articular cartilage, synovial membranes, ligaments and an articular capsule. Together, these tissues give each... (Review)
Review
Limb synovial joints are intricate structures composed of articular cartilage, synovial membranes, ligaments and an articular capsule. Together, these tissues give each joint its unique shape, organization and biomechanical function. Articular cartilage itself is rather complex and organized in distinct zones, including the superficial zone that produces lubricants and contains stem/progenitor cells. For many years there has been great interest in deciphering the mechanisms by which the joints form and come to acquire such unique structural features and diversity. Decades ago, classic embryologists discovered that the first overt sign of joint formation at each prescribed limb site was the appearance of a dense and compact population of mesenchymal cells collectively called the interzone. Work carried out since then by several groups has provided evidence that the interzone cells actively participate in joint tissue formation over developmental time. This minireview provides a succinct but comprehensive description of the many important recent advances in this field of research. These include studies using various conditional reporter mice to genetically trace and track the origin, fate and possible function of joint progenitor cells; studies on the involvement and roles in signaling pathways and transcription factors in joint cell determination and functioning; and studies using advanced methods of gene expression analyses to uncover novel genetic determinants of joint formation and diversity. The overall advances are impressive, and the findings are not only of obvious interest and importance but also have major implications in the conception of future translational medicine tools to repair and regenerate defective, overused or aging joints.
Topics: Animals; Cartilage, Articular; Cell Differentiation; Chondrogenesis; Embryonic Stem Cells; Humans; Joint Capsule; Joints; Morphogenesis
PubMed: 25172830
DOI: 10.1016/j.matbio.2014.08.006 -
Journal of Orthopaedic Surgery and... Jun 2022Hip arthroscopy for treatment of femoroacetabular impingement (FAI) has developed rapidly and has been shown to significantly decrease pain and improve hip function....
BACKGROUND
Hip arthroscopy for treatment of femoroacetabular impingement (FAI) has developed rapidly and has been shown to significantly decrease pain and improve hip function. However, the relationship between hip capsule characteristics and healing after arthroscopic surgery and changes in patient-reported outcomes scores (PROs) for postoperative pain, function, and symptoms is still uncertain.
METHODS
We retrospectively evaluated consecutive patients who were diagnosed with FAI and underwent hip arthroscopy for treatment in our hospital between May 2018 and November 2020. All patients had preoperative MRI and postoperative MRI at least 6 months after arthroscopy. Hip capsular thickness was measured at the proximal, middle, and distal site of the capsule. PROs and PROs at final follow-up were obtained, including visual analog scale (VAS) for pain and modified Harris Hip Score (mHHS).
RESULTS
A total of 194 patients were included in this study. The mean MRI follow-up time was 14.3 (range, 6-37) months, and the mean clinical follow-up time was 26.1 (range, 12-43) months. Postoperative capsular thickness or net change were not correlated with postoperative PROs and VAS (P > .05). Capsular defect was observed in 17 (8.8%) patients. Patients with capsular defect had a relatively higher BMI (P < .05). Patients with capsular defect had a significant lower mHHS and higher VAS compared with patients with continuous capsule (P < .05). Ninety-one percentage of patients with continuous capsule surpassed minimal clinically important difference (MCID) and 80.8% achieved PASS, but only 58.8% of patients with capsular defect surpassed MCID and 47.1% achieved patient acceptable symptom state (PASS).
CONCLUSIONS
Postoperative capsular thickness may not have influence on the clinical outcomes of hip arthroscopy for treatment of FAI. Some capsule of patients who underwent arthroscopic interportal capsulotomy and repair could not heal. Postoperative capsular continuity had a great impact on the clinical outcomes of hip arthroscopy for FAI. Patients with higher BMI may be more likely to have capsule failure to heal.
Topics: Activities of Daily Living; Arthroscopy; Femoracetabular Impingement; Follow-Up Studies; Hip Joint; Humans; Joint Capsule; Pain; Retrospective Studies; Treatment Outcome
PubMed: 35705973
DOI: 10.1186/s13018-022-03208-z -
BMC Musculoskeletal Disorders Mar 2023Immune and non-immune cells contribute to the pathology of chronic arthritis, and they can contribute to tissue remodeling and repair as well as disease pathogenesis....
BACKGROUND
Immune and non-immune cells contribute to the pathology of chronic arthritis, and they can contribute to tissue remodeling and repair as well as disease pathogenesis. The present research aimed to analyze inflammation and bone destruction/regeneration biomarkers in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), osteoarthritis (OA), and ankylosing spondylitis (AS).
METHODS
Samples were obtained from the inflamed knee of patients with knee arthritis who had been referred for undergoing arthroscopies. The synovial membrane was processed for pathological description, IHC analysis, and quantification of mRNA expression ratio by qRT-PCR. Serum levels of TGF-β1, IL-23, IL-6, IL-17 A, IL-22, Dkk1, Sclerostin, BMP2, BMP4, Wnt1, and Wnt5a were measured by ELISA. All these data were analyzed and compared with the demographic, clinical, blood tests, and radiological characteristics of the patients.
RESULTS
The synovial membrane samples were obtained from 42 patients for IHC, extraction, and purification of RNA for synovial mRNA expression analysis, and serum for measuring protein levels from 38 patients. IHC reactivity for TGF-β1 in the synovial tissue was higher in patients with psoriatic arthritis (p 0.036) and was positively correlated with IL-17 A (r = 0.389, p = 0.012), and Dkk1 (r = 0.388, p = 0.012). Gene expression of the IL-17 A was higher in PsA patients (p = 0.018) and was positively correlated with Dkk1 (r = 0.424, p = 0.022) and negatively correlated with BMP2 (r = -0.396, p = 0.033) and BMP4 (r = -0.472, p = 0.010). It was observed that IHC reactivity for TGF-β1 was higher in patients with erosive PsA (p = 0.024).
CONCLUSIONS
The IHC reactivity of TGF-β1 in synovial tissue was higher in patients with erosive psoriatic arthritis, and TGF-β1 was in relation to higher levels of gene expression of IL-17 A and Dkk1.
Topics: Humans; Arthritis, Psoriatic; Transforming Growth Factor beta1; Interleukin-17; Synovial Fluid; Immunohistochemistry; Synovial Membrane; RNA, Messenger
PubMed: 36997896
DOI: 10.1186/s12891-023-06339-4 -
Frontiers in Immunology 2021Effective treatment of osteoarthritis (OA) remains a huge clinical challenge despite major research efforts. Different tissues and cell-types within the joint contribute... (Review)
Review
Effective treatment of osteoarthritis (OA) remains a huge clinical challenge despite major research efforts. Different tissues and cell-types within the joint contribute to disease pathogenesis, and there is great heterogeneity between patients in terms of clinical features, genetic characteristics and responses to treatment. Inflammation and the most abundant immune cell type within the joint, macrophages, have now been recognised as possible players in disease development and progression. Here we discuss recent findings on the involvement of synovial inflammation and particularly the role of synovial macrophages in OA pathogenesis. Understanding macrophage involvement may hold the key for improved OA treatments.
Topics: Animals; Biomarkers; Cartilage; Cell Plasticity; Disease Susceptibility; Humans; Joint Capsule; Macrophage Activation; Macrophages; Osteoarthritis
PubMed: 34211470
DOI: 10.3389/fimmu.2021.678757 -
Diagnostic and Interventional Imaging 2016Tumors and tumor-like lesions of the knee are common conditions. Because the synovial membrane covers a large part of the knee, tumors and tumor-like lesions of the knee... (Review)
Review
Tumors and tumor-like lesions of the knee are common conditions. Because the synovial membrane covers a large part of the knee, tumors and tumor-like lesions of the knee are mostly synovial. Magnetic resonance imaging (MRI) plays a major role in the assessment and characterization of these lesions. However, the diagnostic approach of these lesions must be performed systematically. First, the lesion must be precisely located, and then the anatomical structure involved must be determined. Finally, clinical background that includes the age of the patient, frequency of the disease and, if any, associated signs as well as MRI characteristics must be analyzed. In this review, we describe the anatomy of the knee and its compartments and provide a description of the main tumors and tumor-like lesions of the knee. We present a diagnostic approach based on the location within the knee of the lesions and the anatomical structures involved.
Topics: Chondromatosis, Synovial; Cysts; Hemangioma; Humans; Knee Joint; Lipoma; Magnetic Resonance Imaging; Sarcoma, Synovial; Synovial Membrane; Synovitis, Pigmented Villonodular
PubMed: 27397886
DOI: 10.1016/j.diii.2016.06.004