Role of Paravertebral muscle myostatin upregulation in the development of idiopathic scoliosis

Paravertebral muscle (PVM) abnormalities play important roles in the pathogenesis of idiopathic scoliosis (IS), and elevated oxidative stress could result in PVM injury in IS patients, but the underlying mechanism of oxidative stress generation is still unclear. Increased apoptosis, impaired myogenesis and elevated oxidative stress were found in primary skeletal muscle mesenchymal progenitor cells (hSM-MPCs), which are essential for the myogenesis process of vertebrate skeletal muscles, of IS patients. Through RNA-sequencing and further analysis, we identified significantly upregulated myostatin (MSTN) in IS hSM-MPCs. Overexpression of MSTN in hSM-MPCs from control patients increased the expression of NADPH oxidase 4, promoted reactive oxygen species production and apoptosis, and suppressed myogenesis. However, MSTN knockdown decreased the expression of NADPH oxidase 4, inhibited reactive oxygen species production and apoptosis, and enhanced myogenesis in IS hSM-MPCs. In addition, overexpression of MSTN in the PVMs of mice induced elevated oxidative stress and scoliosis without abnormal vertebral structure. Altogether, our study suggested that abnormal PVM changes and accumulated oxidative stress in IS patients may result from upregulation of MSTN, which could contribute to the development of IS.