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Journal of Orthopaedic Research :... Aug 2017Joint pathology and degeneration is a significant cause of pain. The synovial membrane plays an important role in maintenance of the joint, contributes to the pathology... (Review)
Review
Joint pathology and degeneration is a significant cause of pain. The synovial membrane plays an important role in maintenance of the joint, contributes to the pathology of many arthropathies and may be adversely affected in joint disease. Improving knowledge of the receptors present within the synovium will aid in a better understanding of joint pathology and the development of new treatments for diseases such as osteoarthritis and rheumatoid arthritis. Knowledge of the location and function of synovial membrane receptors (both in healthy and diseased synovium) may provide important targets in the treatment of various arthropathies. Classic pain receptors such as opioid receptors in the synovium are a mainstay in local and systemic management of chronic pain in many species. In addition to these, many other receptors such as bradykinin, neurokinin, transient receptor potential vanilloid, and inflammatory receptors, such as prostanoid and interleukin receptors have been discovered within the synovial membrane. These receptors are important in pain, inflammation, and in maintenance of normal joint function and may serve as targets for pharmacologic intervention in pathologic states. The goal of this review is to outline synovial membrane receptor localization and local therapeutic modulation of these receptors, in order to stimulate further research into pharmacological management of arthropathies at the local level. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1589-1605, 2017.
Topics: Animals; Humans; Joint Diseases; Molecular Targeted Therapy; Receptors, Cell Surface; Receptors, Cytoplasmic and Nuclear; Synovial Membrane
PubMed: 28374922
DOI: 10.1002/jor.23568 -
Stem Cell Research & Therapy Sep 2020Mesenchymal stem cells (MSCs) can be isolated from not only bone marrow, but also various adult mesenchymal tissues such as periosteum, skeletal muscle, and adipose... (Review)
Review
Mesenchymal stem cells (MSCs) can be isolated from not only bone marrow, but also various adult mesenchymal tissues such as periosteum, skeletal muscle, and adipose tissue. MSCs from different tissue sources have different molecular phenotypes and differentiation potential. Synovial membrane (SM) is an important and highly specific component of synovial joints. Previous studies have suggested that the synovium is a structure with a few cell layers thick and consists mainly of fibroblast-like synoviocytes (FLS), which forms a layer that lining the synovial membrane on the joint cavity and synovial fluid through cell-cell contact. In recent years, studies have found that there are also mesenchymal stem cells in the synovium, and as an important part of the mesenchymal stem cell family, it has strong capabilities of cartilage forming and tissue repairing. This article reviews the sources, surface markers, subtypes, influencing factors, and applications in inflammatory joints of synovial membrane mesenchymal stem cells (SM-MSCs) in recent years, aiming to clarify the research status and existing problems of SM-MSCs.
Topics: Adult; Cell Differentiation; Chondrogenesis; Humans; Joint Diseases; Mesenchymal Stem Cells; Synovial Fluid; Synovial Membrane
PubMed: 32894205
DOI: 10.1186/s13287-020-01885-3 -
Seminars in Immunopathology Jun 2017Synovial immunopathology in rheumatoid arthritis is complex involving both resident and infiltrating cells. The synovial tissue undergoes significant neovascularization,... (Review)
Review
Synovial immunopathology in rheumatoid arthritis is complex involving both resident and infiltrating cells. The synovial tissue undergoes significant neovascularization, facilitating an influx of lymphocytes and monocytes that transform a typically acellular loose areolar membrane into an invasive tumour-like pannus. The microvasculature proliferates to form straight regularly-branching vessels; however, they are highly dysfunctional resulting in reduced oxygen supply and a hypoxic microenvironment. Autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies are found at an early stage, often before arthritis has developed, and they have been implicated in the pathogenesis of RA. Abnormal cellular metabolism and mitochondrial dysfunction thus ensue and, in turn, through the increased production of reactive oxygen species actively induce inflammation. Key pro-inflammatory cytokines, chemokines and growth factors and their signalling pathways, including nuclear factor κB, Janus kinase-signal transducer, are highly activated when immune cells are exposed to hypoxia in the inflamed rheumatoid joint show adaptive survival reactions by activating. This review attempts to highlight those aberrations in the innate and adaptive immune systems including the role of genetic and environmental factors, autoantibodies, cellular alterations, signalling pathways and metabolism that are implicated in the pathogenesis of RA and may therefore provide an opportunity for therapeutic intervention.
Topics: Animals; Arthritis, Rheumatoid; Autoantibodies; Disease Susceptibility; Environment; Genetic Predisposition to Disease; Humans; Hypoxia; Signal Transduction; Synovial Membrane
PubMed: 28508153
DOI: 10.1007/s00281-017-0633-1 -
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 -
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 -
Annals of the Rheumatic Diseases Dec 2023Transcriptomic profiling of synovial tissue from patients with early, untreated rheumatoid arthritis (RA) was used to explore the ability of unbiased, data-driven...
OBJECTIVES
Transcriptomic profiling of synovial tissue from patients with early, untreated rheumatoid arthritis (RA) was used to explore the ability of unbiased, data-driven approaches to define clinically relevant subgroups.
METHODS
RNASeq was performed on 74 samples, with disease activity data collected at inclusion. Principal components analysis (PCA) and unsupervised clustering were used to define patient clusters based on expression of the most variable genes, followed by pathway analysis and inference of relative abundance of immune cell subsets. Histological assessment and multiplex immunofluorescence (for CD45, CD68, CD206) were performed on paraffin sections.
RESULTS
PCA on expression of the (n=894) most variable genes across this series did not divide samples into distinct groups, instead yielding a continuum correlated with baseline disease activity. Two patient clusters (PtC1, n=52; PtC2, n=22) were defined based on expression of these genes. PtC1, with significantly higher disease activity and probability of response to methotrexate therapy, showed upregulation of immune system genes; PtC2 showed upregulation of lipid metabolism genes, described to characterise tissue resident or M2-like macrophages. In keeping with these data, M2-like:M1-like macrophage ratios were inversely correlated with disease activity scores and were associated with lower synovial immune infiltration and the presence of thinner, M2-like macrophage-rich synovial lining layers.
CONCLUSION
In this large series of early, untreated RA, we show that the synovial transcriptome closely mirrors clinical disease activity and correlates with synovial inflammation. Intriguingly, lower inflammation and disease activity are associated with higher ratios of M2:M1 macrophages, particularly striking in the synovial lining layer. This may point to a protective role for tissue resident macrophages in RA.
Topics: Humans; Transcriptome; Synovitis; Arthritis, Rheumatoid; Synovial Membrane; Inflammation
PubMed: 37507201
DOI: 10.1136/ard-2023-224068 -
Rheumatology International Apr 2015Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, joint tenderness, and destruction of synovial joints, leading to severe... (Review)
Review
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, joint tenderness, and destruction of synovial joints, leading to severe disability and premature mortality. RA is a multifactorial disease with genetic, environmental, and stochastic components related to its susceptibility. It has been demonstrated that the expression of osteopontin (OPN) is upregulated in the RA patients. Numerous studies have indicated that the full-length OPN or even OPN fragments, such as thrombin-cleaved OPN and its receptors, play the key roles in RA pathogenesis. Therapeutic application of siRNA to target OPN or neutralizing antibodies related to OPN epitopes in RA animal models are in progress, and some results are encouraging. However, there is a long way to go along with the clinical trials. This review focuses on the recent development in research associated with the OPN role in the pathogenesis of RA and provides insights concerning the OPN targeting as therapeutic approaches for patients with RA.
Topics: Animals; Arthritis, Rheumatoid; Cartilage, Articular; Humans; Osteopontin; Synovial Membrane
PubMed: 25163663
DOI: 10.1007/s00296-014-3122-z -
Seminars in Immunology Dec 2021Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease. RA mainly affects synovial joints, with inflammation of the synovial membrane (synovitis),... (Review)
Review
Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease. RA mainly affects synovial joints, with inflammation of the synovial membrane (synovitis), characterised by neo-angiogenesis, hyperplasia of lining layer, and immune cell infiltration that drive local inflammation and, if untreated, can lead to joint destruction and disability. In parallel to the well-known clinical heterogeneity, the underlying synovitis can also be significantly heterogeneous, both at cellular and molecular level, which can at least in part explain why despite the availability of highly effective treatment options, a large proportion of patients are resistant to some individual treatments. The assimilation of recent high-throughput data from analysis at the single-cell level with rigorous and high-quality clinical outcomes obtained from large randomised clinical trials support the definition of disease and treatment response endotypes. Looking ahead, the integration of histological and molecular signatures from the diseased tissue into clinical algorithms may help decision making in the management of patients with Rheumatoid Arthritis in clinical practice.
Topics: Humans; Arthritis, Rheumatoid; Synovitis; Synovial Membrane
PubMed: 35033462
DOI: 10.1016/j.smim.2021.101519 -
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 -
Cellular and Molecular Life Sciences :... Apr 2022Osteoarthritis (OA) synovial membrane is mainly characterized by low-grade inflammation, hyperplasia with increased cell proliferation and fibrosis. We previously...
Osteoarthritis (OA) synovial membrane is mainly characterized by low-grade inflammation, hyperplasia with increased cell proliferation and fibrosis. We previously underscored a critical role for CEMIP in fibrosis of OA cartilage. However, its role in OA synovial membrane remains unknown. An in vitro model with fibroblast-like synoviocytes from OA patients and an in vivo model with collagenase-induced OA mice were used to evaluate CEMIP-silencing effects on inflammation, hyperplasia and fibrosis. Our results showed that i. CEMIP expression was increased in human and mouse inflamed synovial membrane; ii. CEMIP regulated the inflammatory response pathway and inflammatory cytokines production in vitro and in vivo; iii. CEMIP induced epithelial to mesenchymal transition pathway and fibrotic markers in vitro and in vivo; iv. CEMIP increased cell proliferation and synovial hyperplasia; v. CEMIP expression was increased by inflammatory cytokines and by TGF-β signaling; vi. anti-fibrotic drugs decreased CEMIP expression. All these findings highlighted the central role of CEMIP in OA synovial membrane development and underscored that targeting CEMIP could be a new therapeutic approach.
Topics: Animals; Cytokines; Epithelial-Mesenchymal Transition; Fibrosis; Humans; Hyaluronoglucosaminidase; Hyperplasia; Inflammation; Mice; Osteoarthritis; Synovial Membrane
PubMed: 35474501
DOI: 10.1007/s00018-022-04282-6