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• W2170146627 abstract "Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder that primarily affects the joints and results in the progressive destruction of articular structures, particularly cartilage and bone. Notably, the joint destruction is a prominent feature of disease that not only distinguishes RA from other arthritides but also determines its outcome in the majority of affected individuals.Synovial fibroblasts in the most superficial lining layer of the hyperplastic RA synovium have been assigned an important role in the pathogenesis of RA and associated with key processes leading to the degradation of extracellular matrix. It has been understood that these cells exhibit an altered morphology and are characterised by changes in their behaviour that show certain similarities to tumours. Therefore, the phenotype of these cells has been termed “transformed appearing”, “tumour-like”1 or—reflecting the clear differences with malignancies—“activated”. As part of a cellular network, RA synovial fibroblasts are involved in the destruction of extracellular matrix both by direct mechanisms and through interaction with neighbouring cells such as macrophages. Thus, it has been demonstrated that RA synovial fibroblasts release large amounts of the ligand for the receptor activator of nuclear factor β (RANKL), which mediates the differentiation of bone resorbing osteoclasts from their macrophage precursors.2 Direct degradation of extracellular matrix by RA synovial fibroblasts is mediated through the attachment to cartilage and subsequent release of matrix degrading enzymes, particularly matrix metalloproteinases (MMPs) and cathepsins.3Although inflammatory cytokines such as tumour necrosis factor α (TNFα) have been demonstrated to stimulate RA synovial fibroblasts to produce such matrix degrading enzymes, the activation of these RA synovial fibroblasts is maintained even in the absence of continuous stimulation by proinflammatory factors. This notion is derived from different in vitro studies as well as from data on the severe combined immunodeficient (SCID) mouse model of rheumatoid …" @default.
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• W2170146627 date "2005-11-01" @default.
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• W2170146627 title "Are fibroblasts involved in joint destruction?" @default.
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• W2170146627 doi "https://doi.org/10.1136/ard.2005.042424" @default.
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