Abstract
IntroductionFibronectin fragments have been found in the articular cartilage and synovial fluid of patients with osteoarthritis and rheumatoid arthritis. These matrix fragments can stimulate production of multiple mediators of matrix destruction, including various cytokines and metalloproteinases. The purpose of this study was to discover novel mediators of cartilage destruction using fibronectin fragments as a stimulus.MethodsHuman articular cartilage was obtained from tissue donors and from osteoarthritic cartilage removed at the time of knee replacement surgery. Enzymatically isolated chondrocytes in serum-free cultures were stimulated overnight with the 110 kDa α5β1 integrin-binding fibronectin fragment or with IL-1, IL-6, or IL-7. Cytokines and matrix metalloproteinases released into the media were detected using antibody arrays and quantified by ELISA. IL-7 receptor expression was evaluated by flow cytometry, immunocytochemical staining, and PCR.ResultsIL-7 was found to be produced by chondrocytes treated with fibronectin fragments. Compared with cells isolated from normal young adult human articular cartilage, increased IL-7 production was noted in cells isolated from older adult tissue donors and from osteoarthritic cartilage. Chondrocyte IL-7 production was also stimulated by combined treatment with the catabolic cytokines IL-1 and IL-6. Chondrocytes were found to express IL-7 receptors and to respond to IL-7 stimulation with increased production of matrix metalloproteinase-13 and with proteoglycan release from cartilage explants.ConclusionThese novel findings indicate that IL-7 may contribute to cartilage destruction in joint diseases, including osteoarthritis.
Highlights
Fibronectin fragments have been found in the articular cartilage and synovial fluid of patients with osteoarthritis and rheumatoid arthritis
Human articular cartilage was obtained from tissue donors and from osteoarthritic cartilage removed at the time of knee replacement surgery
Compared with cells isolated from normal young adult human articular cartilage, increased IL7 production was noted in cells isolated from older adult tissue donors and from osteoarthritic cartilage
Summary
Fibronectin fragments have been found in the articular cartilage and synovial fluid of patients with osteoarthritis and rheumatoid arthritis. These matrix fragments can stimulate production of multiple mediators of matrix destruction, including various cytokines and metalloproteinases. There is increasing evidence that cytokines, including IL-1, IL-6, and tumor necrosis factor (TNF)-α, play a role in matrix destruction by enhancing chondrocyte catabolic activity [2]. A role for local production of cytokines in the joint destruction that occurs in rheumatoid arthritis (RA) is well established, and there is increasing evidence for the role of cytokines in OA [7]. Determining which cytokines are responsible for joint tissue destruction in arthritis is the subject of continuing research
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