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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 -
Arthritis Research & Therapy 2007Inflammation and degradation of bone are two closely linked processes. Chronic inflammatory arthritis not only leads to inflammatory bone loss but it also involves local... (Review)
Review
Inflammation and degradation of bone are two closely linked processes. Chronic inflammatory arthritis not only leads to inflammatory bone loss but it also involves local erosion of articular bone. This osteo-destructive feature of chronic inflammatory arthritis is a major cause of disability in patients with rheumatoid arthritis. Osteoclasts are essential for the resorption of mineralized cartilage and subchondral bone in chronic arthritis. The observed up-regulation of osteoclast differentiation factors (receptor activator of nuclear factor-kappaB ligand [RANKL]) in the synovial membrane of chronically inflamed joints indicates that osteoclasts are abundant in this setting, leading to rapid degradation of mineralized tissue. Blockade of osteoclast formation is thus a key strategy in preventing structural damage in arthritis. Denosumab, a humanized antibody that neutralizes RANKL, is an attractive candidate agent to inhibit inflammatory bone loss.
Topics: Animals; Arthritis, Rheumatoid; Bone and Bones; Humans; RANK Ligand; Synovial Membrane
PubMed: 17634141
DOI: 10.1186/ar2166 -
Arthritis Research 2001This review focuses on the mechanisms of stress response in the synovial tissue of rheumatoid arthritis. The major stress factors, such as heat stress, shear stress,... (Review)
Review
This review focuses on the mechanisms of stress response in the synovial tissue of rheumatoid arthritis. The major stress factors, such as heat stress, shear stress, proinflammatory cytokines and oxidative stress, are discussed and reviewed, focusing on their potential to induce a stress response in the synovial tissue. Several pathways of stress signalling molecules are found to be activated in the synovial membrane of rheumatoid arthritis; of these the most important examples are heat shock proteins, mitogen-activated protein kinases, stress-activated protein kinases and molecules involved in the oxidative stress pathways. The expression of these pathways in vitro and in vivo as well as the consequences of stress signalling in the rheumatoid synovium are discussed. Stress signalling is part of a cellular response to potentially harmful stimuli and thus is essentially involved in the process of synovitis. Stress signalling pathways are therefore new and promising targets of future anti-rheumatic therapies.
Topics: Animals; Arthritis, Rheumatoid; Cytokines; Heat-Shock Proteins; Humans; Mitogen-Activated Protein Kinases; Oxidative Stress; Stress, Mechanical; Stress, Physiological; Synovial Membrane
PubMed: 11178114
DOI: 10.1186/ar144 -
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 -
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 -
Molecular & Cellular Proteomics : MCP May 2023Rheumatoid arthritis (RA) is a typical autoimmune disease characterized by synovial inflammation, synovial tissue hyperplasia, and destruction of bone and cartilage....
Rheumatoid arthritis (RA) is a typical autoimmune disease characterized by synovial inflammation, synovial tissue hyperplasia, and destruction of bone and cartilage. Protein glycosylation plays key roles in the pathogenesis of RA but in-depth glycoproteomics analysis of synovial tissues is still lacking. Here, by using a strategy to quantify intact N-glycopeptides, we identified 1260 intact N-glycopeptides from 481 N-glycosites on 334 glycoproteins in RA synovium. Bioinformatics analysis revealed that the hyper-glycosylated proteins in RA were closely linked to immune responses. By using DNASTAR software, we identified 20 N-glycopeptides whose prototype peptides were highly immunogenic. We next calculated the enrichment scores of nine types of immune cells using specific gene sets from public single-cell transcriptomics data of RA and revealed that the N-glycosylation levels at some sites, such as IGSF10_N2147, MOXD2P_N404, and PTCH2_N812, were significantly correlated with the enrichment scores of certain immune cell types. Furthermore, we showed that aberrant N-glycosylation in the RA synovium was related to increased expression of glycosylation enzymes. Collectively, this work presents, for the first time, the N-glycoproteome of RA synovium and describes immune-associated glycosylation, providing novel insights into RA pathogenesis.
Topics: Humans; Arthritis, Rheumatoid; Glycopeptides; Glycoproteins; Glycosylation; Osteoarthritis; Proteomics; Synovial Membrane; Proteome
PubMed: 37019382
DOI: 10.1016/j.mcpro.2023.100540 -
Frontiers in Immunology 2022Synovial inflammation in knee osteoarthritis (OA) causes disorganized synovial angiogenesis and complement activation in synovial fluid, but links between complement and...
PURPOSE
Synovial inflammation in knee osteoarthritis (OA) causes disorganized synovial angiogenesis and complement activation in synovial fluid, but links between complement and synovial microvascular pathology have not been established. Since complement causes vascular pathology in other diseases and since sex-differences exist in complement activation and in OA, we investigated sex differences in synovial fluid complement factors, synovial tissue vascular pathology, and associations between complement and synovial vascular pathology in patients with late-stage knee OA.
METHODS
Patients with symptomatic, late-stage radiographic knee OA undergoing total knee arthroplasty or high tibial osteotomy provided matched synovial fluid and tissue biopsies during surgery. Complement factors (C2, C5, adipsin, MBL, and CFI) and terminal complement complex (sC5b-C9) were measured in synovial fluid by multiplex or enzyme-linked immunosorbent assay, respectively. Features of synovial vascular pathology (vascularization, perivascular edema, and vasculopathy) were assessed by histopathology. Multivariate linear regression models were used to assess associations between synovial fluid complement factors and histopathological features of vascular pathology, with adjustment for age, sex, body mass index, and sex interaction. Sex-disaggregated comparisons were completed.
RESULTS
Synovial fluid biomarker and histopathology data were included from 97 patients. Most synovial fluid complement factors and synovial tissue histopathological features were similar between sexes. Synovial fluid C5 trended to lower levels in males (-20.93 ng/mL [95%CI -42.08, 0.23] 0.05). Median vasculopathy scores (0.42 [95%CI 0.07, 0.77] 0.02) were higher in males. In the full cohort, C5 concentration was associated with lower vascularization scores (-0.005 [95%CI -0.010, -0.0001] 0.04) while accounting for sex*C5 interaction. In sex-disaggregated analyses, increased C5 concentration was associated with lower vascularization scores (-0.005 [95%CI -0.009, -0.0001] 0.04) in male patients, but not in female patients. Males had higher sC5b-C9 compared to females. Additionally, males with high C5 had a higher synovial fluid concentration of sC5b-C9 compared to males with low C5. No differences were found in females.
CONCLUSION
Higher synovial fluid C5 levels were associated with increased complement activation and decreased synovial vascularization in males but not in females with OA. Future studies should test whether synovial fluid complement activation suppresses synovial angiogenesis and identify mechanisms accounting for C5-related sex-differences in synovial fluid complement activation in patients with knee OA.
Topics: Complement Activation; Female; Humans; Male; Osteoarthritis, Knee; Sex Characteristics; Synovial Fluid; Synovial Membrane
PubMed: 35686134
DOI: 10.3389/fimmu.2022.890094 -
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 -
Clinical and Experimental Immunology Aug 2019Rheumatoid arthritis is characterized by synovial proliferation, neovascularization and leucocyte extravasation leading to joint destruction and functional disability.... (Review)
Review
Rheumatoid arthritis is characterized by synovial proliferation, neovascularization and leucocyte extravasation leading to joint destruction and functional disability. The blood vessels in the inflamed synovium are highly dysregulated, resulting in poor delivery of oxygen; this, along with the increased metabolic demand of infiltrating immune cells and inflamed resident cells, results in the lack of key nutrients at the site of inflammation. In these adverse conditions synovial cells must adapt to generate sufficient energy to support their proliferation and activation status, and thus switch their cell metabolism from a resting regulatory state to a highly metabolically active state. This alters redox-sensitive signalling pathways and also results in the accumulation of metabolic intermediates which, in turn, can act as signalling molecules that further exacerbate the inflammatory response. The RA synovium is a multi-cellular tissue, and while many cell types interact to promote the inflammatory response, their metabolic requirements differ. Thus, understanding the complex interplay between hypoxia-induced signalling pathways, metabolic pathways and the inflammatory response will provide better insight into the underlying mechanisms of disease pathogenesis.
Topics: Arthritis, Rheumatoid; Cell Hypoxia; Dendritic Cells; Humans; Inflammation; Macrophages; Neovascularization, Pathologic; Signal Transduction; Synovial Membrane; Synoviocytes; T-Lymphocytes
PubMed: 30357805
DOI: 10.1111/cei.13228 -
Folia Morphologica Aug 2013Chondrocytes differentiate from mesenchymal progenitors and produce templates(anlagen) for the developing bones. Chondrocyte differentiation is controlled by Sox... (Review)
Review
Chondrocytes differentiate from mesenchymal progenitors and produce templates(anlagen) for the developing bones. Chondrocyte differentiation is controlled by Sox transcription factors. Templates for the neighbour bones are subsequently separated by conversion of differentiated chondrocytes into non-chondrogenic cells and emergence of interzone in which joints cavitation occurs. A central role in initiating synovial joint formation plays Wnt-14/beta-catenin signalling pathway.Moreover, bone morphogenetic proteins and growth and differentiation factors are expressed at the site of joint formation. Joint cavitation is associated with increased hyaluronic acid synthesis. Hyaluronic acid facilitates tissue separation and creation of a functional joint cavity. According to the traditional view articular cartilage represents part of cartilage anlage that is not replaced by bone through endochondral ossification. Recent studies indicate, however, that peri-joint mesenchymal cells take part in interzone formation and that these interzone cells subsequently differentiate into articular chondrocytes and synovial cells. Thus,anlage chondrocytes have a transient character and disappear after cessation of growth plate function while articular chondrocytes have stable and permanent phenotype and function throughout life.
Topics: Animals; Cartilage, Articular; Chondrocytes; Humans; Joints; Synovial Membrane
PubMed: 24068678
DOI: 10.5603/fm.2013.0031