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Myostatin induces tumor necrosis factor‐α expression in rheumatoid arthritis synovial fibroblasts through the PI3K–Akt signaling pathway

In rheumatoid arthritis (RA), a chronic inflammatory disease, loss of muscle mass is an important contributor to the loss of muscle strength in RA patients. Myostatin, a myokine involved in the process of muscle hypertrophy and myogenesis, enhances osteoclast differentiation and inflammation. Here, we investigated the mechanisms of myostatin in RA synovial inflammation. We found a positive correlation between myostatin and tumor necrosis factor‐α (TNF‐α), a well‐known proinflammatory cytokine, in RA synovial tissue. Our in vitro results also showed that myostatin dose‐dependently induced TNF‐α expression through the phosphatidylinositol 3‐kinase (PI3K)–Akt–AP‐1 signaling pathway. Myostatin treatment of human MH7A cells stimulated AP‐1‐induced luciferase activity and activation of the c‐Jun binding site on the TNF‐α promoter. Our results indicated that myostatin increases TNF‐α expression via the PI3K–Akt–AP‐1 signaling pathway in human RA synovial fibroblasts. Myostatin appears to be a promising target in RA therapy.