Department of Spine Surgery, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, Hunan, China, 410008.
Int J Biol Sci. 2019 Sep 7;15(12):2584-2595. doi: 10.7150/ijbs.33340. eCollection 2019.
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 and . 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 and the important myogenesis regulator 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 and . 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.
特发性脊柱侧凸（IS）是一种病因不明的疾病，其特征是脊柱旋转不对称。描述 IS 患者的组织化学和病理学分析的报告表明，脊柱旁肌肉的顶点发生了坏死、纤维化和脂肪萎缩。然而，关于 IS 患者与匹配对照组的脊柱旁肌肉变化的研究很少；因此，IS 患者脊柱旁肌肉损伤的基本机制仍不清楚。在这项研究中，我们研究了对照组和 IS 患者的脊柱旁肌肉的形态变化，并检查了可能的机制。与对照组相比，IS 患者的脊柱旁肌肉顶点两侧的肌纤维坏死增加，TUNEL 阳性凋亡细胞的数量也增加。与对照组相比，IS 患者的凋亡信号通路，包括促凋亡蛋白如 cleaved-caspase 3 和细胞色素 c，明显上调，而抗凋亡 Bcl-2/Bax 则明显下调。此外，PGC-1α 和 SOD1 的上调与 IS 患者中 ROS 产生的增加一致。IS 患者的肌纤维类型分布以及 IIa 型肌纤维标志物和重要的肌生成调节因子的 mRNA 水平也发生了显著变化。此外，在无糖和无血清培养条件下用抗霉素 A 处理的 C2C12 或人骨骼肌间充质祖细胞，可激活氧化应激并诱导细胞凋亡，显示出相似的肌纤维类型分布变化模式和下调和。总的来说，我们的研究表明，与对照组相比，IS 患者的肌肉损伤程度和积累的氧化应激程度增加，并且在 IS 患者中也观察到异常的肌生成。由于氧化应激的增加可导致肌肉细胞凋亡和肌生成失调，它可能与 IS 患者的病理变化有关，并有助于 IS 的发展和进展。
