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• W2003208357 abstract "Abstract Objective To determine whether proinflammatory cytokine treatment or the complete absence of select cytokines modulates the expression of RANKL and osteoprotegerin (OPG) in synovial fibroblasts. Methods Fibroblasts were isolated from normal and rheumatoid human synovium and from normal or arthritic joints of wild‐type and cytokine gene–deficient (interleukin‐4–knockout [IL‐4 −/− ] and interferon‐γ–knockout [IFNγ −/− ]) mice. Fibroblasts were stimulated with proinflammatory cytokines (tumor necrosis factor α [TNFα], IL‐1β, and IL‐17) or antiosteoclastogenic cytokines (IL‐4 and IFNγ), alone or in combination, and the expression of RANKL and OPG was measured. Results Proinflammatory cytokine–stimulated fibroblasts from rheumatoid and arthritic mouse joints expressed higher levels of RANKL and OPG than those from normal joints. IL‐4 suppressed RANKL expression and increased OPG expression, IFNγ reduced the production of both RANKL and OPG, and IL‐17 had only a modest effect on the expression of RANKL or OPG. Additive effects of combination treatment (TNFα/IL‐17 or IL‐1β/IL‐17) were observed only in the human system. Extensive destruction was observed in the arthritic joints of IL‐4 −/− mice, with a corresponding upward shift of the RANKL:OPG ratios. However, an IL‐17 deficiency did not attenuate arthritis or reduce bone resorption. Conclusion Proinflammatory cytokines induce the expression of RANKL and OPG in both human and murine synovial fibroblasts. The RANKL:OPG ratios are shifted in favor of bone protection by IL‐4 treatment, and, to a lesser extent, by IFNγ treatment. Unexpectedly, an IL‐17 deficiency alone does not induce reduced inflammatory bone destruction. Our results suggest that synovial fibroblasts may significantly contribute to bone resorption through modulation of RANKL and OPG production in a cytokine‐rich milieu of inflamed joints." @default.
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• W2003208357 date "2008-07-30" @default.
• W2003208357 modified "2023-10-16" @default.
• W2003208357 title "Cytokine-controlled RANKL and osteoprotegerin expression by human and mouse synovial fibroblasts: Fibroblast-mediated pathologic bone resorption" @default.
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• W2003208357 doi "https://doi.org/10.1002/art.23653" @default.
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