Molecular basis and therapeutic potential of myostatin on bone formation and metabolism in orthopedic disease

Abstract Myostatin, a member of the transforming growth factor‐β (TGF‐β) superfamily, is a key autocrine/paracrine inhibitor of skeletal muscle growth. Recently, researchers have postulated that myostatin is a negative regulator of bone formation and metabolism. Reportedly, myostatin is highly expressed in the fracture area, affecting the endochondral ossification process during the early stages of fracture healing. Furthermore, myostatin is highly expressed in the synovium of patients with rheumatoid arthritis (RA) and is an effective therapeutic target for interfering with osteoclast formation and joint destruction in RA. Thus, myostatin is a potent anti‐osteogenic factor and a direct modulator of osteoclast differentiation. Evaluation of the molecular pathway revealed that myostatin can activate SMAD and mitogen‐activated protein kinase signaling pathways, inhibiting the Wnt/β‐catenin pathway to synergistically regulate muscle and bone growth and metabolism. In summary, inhibition of myostatin or the myostatin signaling pathway has therapeutic potential in the treatment of orthopedic diseases. This review focused on the effects of myostatin on bone formation and metabolism and discussed the potential therapeutic effects of inhibiting myostatin and its pathways in related orthopedic diseases.