Oncostatin M acting via OSMR, augments the actions of IL-1 and TNF in synovial fibroblasts
Research output: Contribution to journal › Article
OBJECTIVE: To identify how the gp130-signaling cytokine oncostatin M (OSM), acting alone or in concert with IL-1beta or TNFalpha, affects synovial fibroblast expression of genes relevant to inflammation and bone erosion in inflammatory arthritis. METHODS: Synovial fibroblasts (SFs) were isolated from non-arthritic wild type (WT) or OSM receptor deficient (OSMR(-/-)) mice and stimulated with OSM, IL-1beta or TNFalpha and their combinations. Cytokine gene expression was assessed by quantitative RT-PCR. ELISA, flow cytometry and immunohistochemistry identified protein expression. Gene expression patterns were confirmed in SFs isolated from patients with osteoarthritis (OASFs) and rheumatoid arthritis (RASFs). RESULTS: Expression of OSM and its receptors, gp130, OSMR and LIFR, was increased in synovial tissue from the mouse antigen-induced arthritis model. In isolated WT mouse synovial fibroblasts OSM alone, or in synergy with IL-1beta, or together with TNFalpha, potently induced expression of the pro-inflammatory cytokine IL-6. OSM also induced a sustained increase in mRNA levels of the pro-osteoclastic cytokine RANKL. Combining OSM with IL-1beta, but not with TNFalpha, further increased RANKL expression. Importantly these effects of OSM were all dependent on the expression of OSMR. Furthermore, OSM also increased expression of its own receptors, gp130 and OSMR and the IL-1 receptor, IL1-R1; the latter effects were also observed in both human OASFs and RASFs. CONCLUSION: Together our data suggests that OSM signaling via OSMR in SFs has the potential to contribute significantly to joint destruction in inflammatory arthritis. It not only induces expression of pro-inflammatory and pro-osteoclastic cytokines but can also augment its own actions and that of IL-1 by inducing expression of OSMR and IL-1R1.
|Research areas and keywords||
Subject classification (UKÄ) – MANDATORY
|Publication status||Published - 2014|