Shu Qingyang, Yang Guanteng, Tang Mingxing, Guo Chaofeng, Zhang Hongqi, Li Jiong
Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorder, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, Hunan, 410008, China.
Biochem Biophys Res Commun. 2023 Apr 16;652:22-30. doi: 10.1016/j.bbrc.2023.02.034. Epub 2023 Feb 16.
The prevalence of idiopathic scoliosis (IS) is 2-3% worldwide and is more common in girls. Estrogen receptors (ERs) is supposed to be related to sex differences and development of IS. Meanwhile, paravertebral muscle (PVM) abnormalities play important roles in the pathogenesis of IS. But the changes of ERs between the PVMs from IS patients and controls, and the mechanism by which ERs may affect IS patients remain unclear. Thus, the expression levels of ERs, myogenesis regulator (MYOG) and adipogenesis related factors (CEBPA, PPARγ, FABP4), as well as morphological changes in the PVMs and primary skeletal muscle mesenchymal progenitor cells (hSM-MPCs) of IS patients and controls were investigated. Increased expression levels of ERs and CEBPA, PPARγ, FABP4, together with severe myofiber necrosis and fat infiltration, were found in the PVMs of IS patients. Meanwhile, upregulated ERs, FABP4 and CEBPA, downregulated MYOG and impaired myogenesis were also revealed in the hSM-MPCs of IS patients compared with those of controls. Upregulation of ERs inhibited myogenesis but increased expression of CEBPA and FABP4 in C2C12 myoblasts. Nevertheless, treatment of ER antagonist increased expression of MYOG, enhanced myogenesis and decreased expression of CEBPA and FABP4 in skeletal muscle cells of IS patients. Therefore, our study suggested that PVMs specific upregulation of ERs could impair myogenesis and increase the expression of adipogenesis related factors, further leading to PVMs abnormalities in IS patients.
特发性脊柱侧凸（IS）在全球的患病率为2%-3%，在女孩中更为常见。雌激素受体（ERs）被认为与IS的性别差异和发展有关。同时，椎旁肌（PVM）异常在IS的发病机制中起重要作用。但是，IS患者和对照组的PVM之间ERs的变化，以及ERs可能影响IS患者的机制仍不清楚。因此，研究了IS患者和对照组的PVM以及原代骨骼肌间充质祖细胞（hSM-MPCs）中ERs、成肌调节因子（MYOG）和脂肪生成相关因子（CEBPA、PPARγ、FABP4）的表达水平，以及形态学变化。在IS患者的PVM中发现ERs、CEBPA、PPARγ、FABP4的表达水平升高，同时伴有严重的肌纤维坏死和脂肪浸润。同时，与对照组相比，IS患者的hSM-MPCs中ERs、FABP4和CEBPA上调，MYOG下调，成肌受损。在C2C12成肌细胞中，ERs的上调抑制了成肌，但增加了CEBPA和FABP4的表达。然而，用ER拮抗剂治疗可增加IS患者骨骼肌细胞中MYOG的表达，增强成肌，并降低CEBPA和FABP4的表达。因此，我们的研究表明，PVM中ERs的特异性上调可能损害成肌并增加脂肪生成相关因子的表达，进而导致IS患者的PVM异常。
