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Arthritis Research 2002Angiogenesis is a prominent feature of rheumatoid synovitis. Formation of new blood vessels permits a supply of nutrients and oxygen to the augmented inflammatory cell... (Review)
Review
Angiogenesis is a prominent feature of rheumatoid synovitis. Formation of new blood vessels permits a supply of nutrients and oxygen to the augmented inflammatory cell mass and so contributes to perpetuation of joint disease. Vascular endothelial growth factor (VEGF) is a potent endothelial cell-specific growth factor that is upregulated by proinflammatory cytokines and by hypoxia. Serum VEGF concentrations are elevated in rheumatoid arthritis (RA) and correlate with disease activity. Furthermore, serum VEGF measured at first presentation in RA is highly significantly correlated with radiographic progression of disease over the subsequent year. Power Doppler ultrasonography is a sensitive method for demonstrating the presence of blood flow in small vessels and there is a very close relation between the presence or absence of vascular flow signal on power Doppler imaging and the rate of early synovial enhancement on dynamic gadolinium-enhanced magnetic resonance imaging (MRI) of joints with RA. Images obtained by both dynamic enhanced MRI and power Doppler ultrasonography correlate with vascularity of synovial tissue as assessed histologically. In early RA, there is a striking association between joint erosions assessed on high-resolution ultrasonography and vascular signal in power Doppler mode. Collectively, these findings implicate vascular pannus in the erosive phase of disease and strongly suggest that proangiogenic molecules such as VEGF are targets for novel therapies in RA. Animal model data supports this concept. It seems likely that serological and imaging measures of vascularity in RA will become useful tools in the assessment of disease activity and response to therapy.
Topics: Arthritis, Rheumatoid; Blood Vessels; Endothelial Growth Factors; Humans; Intercellular Signaling Peptides and Proteins; Lymphokines; Magnetic Resonance Imaging; Synovial Membrane; Ultrasonography, Doppler; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 12110128
DOI: 10.1186/ar582 -
Arthritis Research 2000Fibroblast-like cells in the synovial lining (type B lining cells), stroma and pannus tissue are targeted by many signals, such as the following: ligands binding to cell... (Review)
Review
Fibroblast-like cells in the synovial lining (type B lining cells), stroma and pannus tissue are targeted by many signals, such as the following: ligands binding to cell surface receptors; lipid soluble, small molecular weight mediators (eg nitric oxide [NO], prostaglandins, carbon monoxide); extracellular matrix (ECM)-cell interactions; and direct cell-cell contacts, including gap junctional intercellular communication. Joints are subjected to cyclic mechanical loading and shear forces. Adherence and mechanical forces affect fibroblasts via the ECM (including the hyaluronan fluid phase matrix) and the pericellular matrix (eg extracellular matrix metalloproteinase inducer [EMMPRIN]) matrices, thus modulating fibroblast migration, adherence, proliferation, programmed cell death (including anoikis), synthesis or degradation of ECM, and production of various cytokines and other mediators [1]. Aggressive, transformed or transfected mesenchymal cells containing proto-oncogenes can act in the absence of lymphocytes, but whether these cells represent regressed fibroblasts, chondrocytes or bone marrow stem cells is unclear.
Topics: Animals; Arthritis; Cell Communication; Fibroblasts; Humans; Signal Transduction; Synovial Membrane
PubMed: 11094447
DOI: 10.1186/ar111 -
The role of innate immunity in osteoarthritis: when our first line of defense goes on the offensive.The Journal of Rheumatology Mar 2015Although osteoarthritis (OA) has existed since the dawn of humanity, its pathogenesis remains poorly understood. OA is no longer considered a "wear and tear" condition... (Review)
Review
Although osteoarthritis (OA) has existed since the dawn of humanity, its pathogenesis remains poorly understood. OA is no longer considered a "wear and tear" condition but rather one driven by proteases where chronic low-grade inflammation may play a role in perpetuating proteolytic activity. While multiple factors are likely active in this process, recent evidence has implicated the innate immune system, the older or more primitive part of the body's immune defense mechanisms. The roles of some of the components of the innate immune system have been tested in OA models in vivo including the roles of synovial macrophages and the complement system. This review is a selective overview of a large and evolving field. Insights into these mechanisms might inform our ability to identify patient subsets and give hope for the advent of novel OA therapies.
Topics: Humans; Immunity, Innate; Inflammation; Osteoarthritis; Synovial Membrane
PubMed: 25593231
DOI: 10.3899/jrheum.140382 -
International Journal of Molecular... Apr 2024The gradual deterioration of articular cartilage was thought to be the central event in osteoarthritis (OA), but recent studies demonstrated the importance of low-grade...
The gradual deterioration of articular cartilage was thought to be the central event in osteoarthritis (OA), but recent studies demonstrated the importance of low-grade synovitis in the progression of OA. The Syndecan (SDC) family of membrane proteoglycans is known to be involved in the regulation of inflammation, but there is limited evidence considering the role of syndecans in OA synovitis. Our study aimed to investigate the hip OA synovial membrane expression patterns of SDC1, SDC2 and SDC4, as well as exostosins and sulfotransferases (enzymes involved in the polymerisation and modification of syndecans' heparan sulphate chains). Synovial membrane samples of patients with OA (24) were divided into two groups according to their Krenn synovitis score severity. The immunohistochemical expressions of SDC1, SDC2, SDC4, EXT1, EXT2, NDST1 and NDST2 in synovial intima and subintima were then analysed and compared with the control group (patients with femoral neck fracture). According to our study, the immunoexpression of SDC1, NDST1 and EXT2 is significantly increased in the intimal cells of OA synovial membrane in patients with lower histological synovitis scores and SDC4 in patients with higher synovitis scores, in comparison with non-OA controls. The difference in the expression of SDC2 among the OA and non-OA groups was insignificant. SDC1, SDC4, NDST1 and EXT2 seem to be involved as inflammation moderators in low-grade OA synovitis and, therefore, should be further investigated as potential markers of disease progression and therapeutic goals.
Topics: Aged; Female; Humans; Male; Middle Aged; Inflammation; N-Acetylglucosaminyltransferases; Osteoarthritis, Hip; Sulfotransferases; Syndecans; Synovial Membrane; Synovitis; Biomarkers
PubMed: 38674142
DOI: 10.3390/ijms25084557 -
Arthritis & Rheumatology (Hoboken, N.J.) Mar 2022Findings from recent transcriptome analyses of the synovium of patients with rheumatoid arthritis (RA) have revealed that 15-fold expanded HLA-DR+CD90+ synovial...
OBJECTIVE
Findings from recent transcriptome analyses of the synovium of patients with rheumatoid arthritis (RA) have revealed that 15-fold expanded HLA-DR+CD90+ synovial fibroblasts potentially act as key mediators of inflammation. The reasons for the expansion of HLA-DR+CD90+ synovial fibroblasts are unclear, but genetic signatures indicate that interferon-γ (IFNγ) plays a central role in the generation of this fibroblast subset. The present study was undertaken to investigate the generation, function and therapeutically intended blockage of HLA-DR+CD90+ synovial fibroblasts.
METHODS
We combined functional assays using primary human materials and focused bioinformatic analyses of mass cytometry and transcriptomics patient data sets.
RESULTS
We detected enriched and activated Fcγ receptor type IIIa-positive (CD16+) NK cells in the synovial tissue from patients with active RA. Soluble immune complexes were recognized by CD16 in a newly described reporter cell model, a mechanism that could be contributing to the activation of natural killer (NK) cells in RA. In vitro, NK cell-derived IFNγ induced HLA-DR on CD90+ synovial fibroblasts, leading to an inflammatory, cytokine-secreting HLA-DR+CD90+ phenotype. HLA-DR+CD90+ synovial fibroblasts consecutively activated CD4+ T cells upon receptor crosslinking via superantigens. HLA-DR+CD90+ synovial fibroblasts also activated CD4+ T cells in the absence of superantigens, an effect that was initiated by NK cell-derived IFNγ and that was 4 times stronger in patients with RA compared to patients with osteoarthritis. Finally, JAK inhibition in synovial fibroblasts prevented HLA-DR induction and blocked proinflammatory signals to T cells.
CONCLUSION
The HLA-DR+CD90+ phenotype represents an activation state of synovial fibroblasts during the process of inflammation in RA that can be induced by IFNγ, likely generated from infiltrating leukocytes such as activated NK cells. The induction of these proinflammatory, interleukin-6-producing, and likely antigen-presenting synovial fibroblasts can be targeted by JAK inhibition.
Topics: Arthritis, Rheumatoid; Fibroblasts; HLA-DR Antigens; Humans; Interferon-gamma; Synovial Fluid; Synovial Membrane; Thy-1 Antigens
PubMed: 34435471
DOI: 10.1002/art.41958 -
Annals of the Royal College of Surgeons... Mar 1948
Topics: Cardiovascular System; Humans; Synovial Membrane
PubMed: 18908969
DOI: No ID Found -
The Tohoku Journal of Experimental... May 2019Synovial fat deposition, also known as lipoma arborescens, is a rare articular disorder with villous synovial proliferation, commonly seen in the knee. We explored the...
Synovial fat deposition, also known as lipoma arborescens, is a rare articular disorder with villous synovial proliferation, commonly seen in the knee. We explored the relationship between the degree of synovial fat deposition on the magnetic resonance imaging (MRI) and the severity of degenerative joint disorder, also called osteoarthritis, on plain radiography. The enrolled patients underwent MRI with a 0.4T permanent magnetic unit in a single institution over a 9-month period. The indications of MRI were chronic knee disorder of non-specific cause. Patients with minor trauma were also included. Consecutive 1,091 knees of 1,075 patients were assessed for the degree of synovial fat deposition on MRI and the severity of degenerative joint disorder on plain radiography. The degenerative joint disorder was graded by radiographic features obtained within one month from MRI using Kellgrene-Lawrence (K-L) scores. MRI features of synovial fat deposition were classified as none, mild and severe. Synovial fat deposition was identified in 30 knees of 29 patients (2.7%) (11 men and 18 women; aged from 25 to 86 years, one patient with bilateral lesions): one female patient with osteoarthritis secondary to rheumatoid arthritis and 28 patients with degenerative joint disorder. The K-L grade was 4 in the case of rheumatoid arthritis. There was a moderate positive correlation between the K-L grade and fat deposition grade (correlation coefficient: 0.59, p < 0.001). Thus, synovial fat deposition was noted in the advanced degenerative joint disorder. We propose that fat deposition represents a nonspecific secondary phenomenon of degenerative joint disorder.
Topics: Adiposity; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Female; Humans; Joint Diseases; Knee Joint; Magnetic Resonance Imaging; Male; Middle Aged; Synovial Membrane; Young Adult
PubMed: 31080194
DOI: 10.1620/tjem.248.13 -
BMC Medical Genetics Mar 2020Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability. This study attempted to investigate the key mRNAs and miRNAs related to OA.
BACKGROUND
Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability. This study attempted to investigate the key mRNAs and miRNAs related to OA.
PATIENTS AND METHODS
From April 17th, 2018 to May 17th, 2018, five patients with OA and three normal controls were enrolled in this present study. To identify the differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) between patients with OA and normal controls, RNA-sequencing was performed. Then, DEmiRNA-target DEmRNAs analysis and functional annotation of DEmiRNA-target DEmRNAs were performed. To validate the RNA-sequencing results, quantitative real time-PCR (RT-PCR) and western blot analysis were performed as well.
RESULTS
A total of 1068 DEmRNAs, 21 DEmiRNAs and 395 DEmiRNA-DEmRNA pairs were identified in synovial tissues of patients with OA. The functional annotation of DEmiRNA-target DEmRNAs revealed that Pathways in cancer and PI3K-Akt signaling pathway were significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. QRT-PCR and western blot results revealed that except for TLR7, the expression level of the others was consistent with the RNA-sequencing results, generally.
CONCLUSION
The findings of this present study may provide new clues for the roles of DEmRNAs and DEmiRNAs in the pathogenesis of OA.
Topics: Case-Control Studies; Disease Progression; Gene Expression Profiling; Gene Expression Regulation; Humans; MicroRNAs; Osteoarthritis; RNA, Messenger; Sequence Analysis, RNA; Synovial Membrane; Exome Sequencing
PubMed: 32122327
DOI: 10.1186/s12881-020-0978-5 -
Annals of the Rheumatic Diseases Dec 1998
Review
Topics: Anti-Inflammatory Agents, Non-Steroidal; Gene Expression; Glucocorticoids; Humans; Hypoxia; Research; Synovial Membrane; Synovitis; Wound Healing
PubMed: 10070268
DOI: 10.1136/ard.57.12.703 -
Journal of Anatomy Mar 2016The lining layer of the synovial membrane in the temporomandibular joint (TMJ) contains two types of lining cells: macrophage-like type A and fibroblast-like type B...
The lining layer of the synovial membrane in the temporomandibular joint (TMJ) contains two types of lining cells: macrophage-like type A and fibroblast-like type B cells. The type B cells are particularly heterogeneous in their morphology and immunoreactivity, so that details of their functions remain unclear. Some of the type B cells exhibit certain resemblances in their ultrastructure to those of an activated capillary pericyte at the initial stage of the angiogenesis. The articular surface, composed of cartilage and the disc in the TMJ, has few vasculatures, whereas the synovial lining layer is richly equipped with blood capillaries to produce the constituent of synovial fluid. The present study investigated at both the light and electron microscopic levels the immunocytochemical characteristics of the synovial lining cells in the adult rat TMJ, focusing on their contribution to the synovial vascularization. It also employed an intravascular perfusion with Lycopersicon esculentum (tomato) lectin to identify functional vessels in vivo. Results showed that several type B cells expressed desmin, a muscle-specific intermediate filament which is known as the earliest protein to appear during myogenesis as well as being a marker for the immature capillary pericyte. These desmin-positive type B cells showed immunoreactions for vimentin and pericyte markers (neuron-glial 2; NG2 and PDGFRβ) but not for the other markers of myogenic cells (MyoD and myogenin) or a contractile apparatus (αSMA and caldesmon). Immunoreactivity for RECA-1, an endothelial marker, was observed in the macrophage-like type A cells. The arterioles and venules inside the synovial folds extended numerous capillaries with RECA-1-positive endothelial cells and desmin-positive pericytes to distribute densely in the lining layer. The distal portion of these capillaries showing RECA-1-immunoreactivity lacked lectin-staining, indicating a loss of blood-circulation due to sprouting or termination in the lining layer. The desmin-positive type B and RECA-1-positive type A cells attached to this portion of the capillaries. Some capillaries in the lining layer also expressed ninein, a marker for sprouting endothelial cells, called tip cells. Since an activated pericyte, macrophage and tip cell are known to act together at the forefront of the vessel sprout during angiogenesis, the desmin-positive type B cell and RECA-1-positive type A cell might serve as these angiogenic cells in the synovial lining layer. Tomato lectin perfusion following decalcification would be a highly useful tool for research on the vasculature of the mineralized tissue. Use of this technique combined with immunohistochemistry should permit future extensive investigations on the presence of the physiological angiogenesis and on the function of the lining cells in the synovial membrane.
Topics: Animals; Immunohistochemistry; Male; Microscopy, Electron; Rats; Rats, Wistar; Synovial Membrane; Temporomandibular Joint
PubMed: 26642772
DOI: 10.1111/joa.12426