Osteopontin Promotes Oncostatin M Production in Human Osteoblasts: Implication of Rheumatoid Arthritis Therapy

摘要: Accumulating evidence indicates that subchondral bone might play an essential role in rheumatoid arthritis (RA). Osteopontin (OPN) induces the production of important proinflammatory cytokine involved pathogenesis RA. This study evaluated activation oncostatin M (OSM) by OPN human primary osteoblasts to understand RA and characterized intracellular signaling pathways this activation. Quantitative PCR, ELISA, Western blot results indicated stimulation with OSM expression through αvβ3 integrin/c-Src/platelet-derived growth factor receptor transactivation/MEK/ERK. Treatment also increased c-Jun phosphorylation, AP-1 luciferase activity, binding element on promoter, as demonstrated using chromatin immunoprecipitation assay. Moreover, inhibition lentiviral-OPN short hairpin RNA resulted amelioration articular swelling, cartilage erosion, ankle joint mice collagen-induced shown microcomputed tomography immunohistochemistry staining. Our imply increases response OPN-induced inflammation vitro. Finally, ameliorates inflammatory destruction arthritis. Therefore, may be a potential therapeutic target for