Int J Biol Sci 2019; 15(12):2584-2595. doi:10.7150/ijbs.33340
Muscle Injury Associated Elevated Oxidative Stress and Abnormal Myogenesis in Patients with Idiopathic Scoliosis
Department of Spine Surgery, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, Hunan, China, 410008.
Li J, Tang M, Yang G, Wang L, Gao Q, Zhang H. Muscle Injury Associated Elevated Oxidative Stress and Abnormal Myogenesis in Patients with Idiopathic Scoliosis. Int J Biol Sci 2019; 15(12):2584-2595. doi:10.7150/ijbs.33340. Available from http://www.ijbs.com/v15p2584.htm
Idiopathic scoliosis (IS) is a disease with unknown etiology characterized by spinal rotation asymmetry. Reports describing the histochemical and pathological analyses of IS patients have shown that necrosis, fibrosis and fatty involution occurred on the apex paraspinal muscles. However, research on the changes in the paraspinal muscles of IS patients compared with those in matched controls is rare; thus, the basic mechanism of how paraspinal muscles are injured in IS patients is still unclear. In this study, we investigated the morphological changes of paraspinal muscles in the control group and IS patients, and the possible mechanisms were examined in vivo and in vitro. Increased myofiber necrosis was found on both sides of the apex paraspinal muscles of IS patients compared with those of the control group, and the number of TUNEL-positive apoptotic cells was also increased. Apoptosis signaling pathways, including pro-apoptosis proteins such as cleaved-caspase 3 and cytochrome c, were markedly upregulated, whereas the anti-apoptotic Bcl-2/Bax was significantly downregulated in IS patients compared with the control group. Moreover, PGC-1α and SOD1 were upregulated in accordance with the increased ROS production in IS patients. The distribution of myofiber types, as well as the mRNA levels of type IIa myofiber marker MYH2 and the important myogenesis regulator MYOG were remarkably changed in IS patients. In addition, C2C12 or human skeletal muscle mesenchymal progenitor cells treated with antimycin A in glucose-free and serum-free culture medium, which can activate oxidative stress and induce apoptosis, showed similar patterns of the changed distribution of myofiber types and downregulation of MYH2 and MYOG. Altogether, our study suggested that the extents of severe muscle injury and accumulated oxidative stress were increased in IS patients compared with the control group, and the abnormal myogenesis was also observed in IS patients. Since elevated oxidative stress can lead to apoptosis and the dysregulation of myogenesis in muscle cells, it may be associated with the pathological changes observed in IS patients and contribute to the development and progression of IS.
Keywords: Idiopathic scoliosis, muscle injury, myogenesis, apoptosis, oxidative stress, ROS