Cytokine-controlled RANKL and osteoprotegerin expression by human and mouse synovial fibroblasts: Fibroblast-mediated pathologic bone resorption

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