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Role of myostatin in joint and bone destruction of rheumatoid arthritis. Exposure of synovial fibroblasts to inflammatory cytokines causes the upregulation of myostatin in patients with RA. Myostatin enhances RANKL-induced osteoclast differentiation in autocrine and paracrine manners. Myostatin stimulates osteoclast formation through increased Smad2-dependent nuclear translocation of NFATc1 and subsequent upregulation of osteoclast differentiation genes.13
