Modulators of Fam210a and roles of Fam210a in myoblastic functions.
Modulators of Fam210a and roles of Fam210a in myoblastic functions.
复制标题
Fam210a 的调节剂以及 Fam210a 在成肌细胞功能中的作用。
DOI：
10.1007/s00223-020-00661-y
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Sugimoto T
中科院分区：
文献类型：
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作者：
Tanaka K;Kanazawa I;Richards JB;Goltzman D;Sugimoto T
Fam210a是一种在小鼠体内调节肌肉质量和力量的新型蛋白。然而，Fam210a对成肌细胞功能以及Fam210a调节剂的详细影响尚不清楚。因此，我们研究了(1)Fam210a在小鼠C2C12细胞成肌细胞分化、增殖、凋亡和降解中的作用，以及(2)调节Fam210a表达的因素。我们发现Fam210a mRNA水平在成肌细胞分化过程中降低。通过siRNA降低内源性Fam210a水平可抑制肌生成因子（Pax7、Myf5、Myogenin和Mhc）和肌肉降解因子（Murf1）的mRNA水平。另一方面，Fam210a siRNA不影响C2C12细胞中凋亡因子Bcl-2和Bax的mRNA编码以及ELISA检测的细胞凋亡程度。相反，Fam210a siRNA增加了诱导破骨细胞发生的Mmp-12的mRNA水平。有趣的是，已知影响细胞代谢和肌肉功能的胰岛素和125 (OH)2D以剂量依赖的方式显著增加了Fam210a mRNA的水平。此外，pi3激酶抑制剂和通过siRNA降低内源性维生素D受体（VDR）水平分别抑制胰岛素和1,25(OH) 2d诱导的Fam210a表达。综上所述，Fam210a可能促进成肌细胞分化和蛋白水解。此外，胰岛素和1,25(OH)2D可能通过增强Fam210a的表达来诱导成肌细胞分化和降解。
Fam210a is a novel protein regulating muscle mass and strength in mice in vivo. However, detailed effects of Fam210a on the function of myoblasts as well as modulators of Fam210a are still unknown. We, thus, investigated (1) the roles of Fam210a in myoblast differentiation, proliferation, apoptosis and degradation, and (2) the factors that regulate Fam210a expression in murine C2C12 cells. We found that the level of Fam210a mRNA was reduced during myoblast differentiation. Reduction in endogenous Fam210a levels by siRNA suppressed mRNA levels of myogenic factors (Pax7, Myf5, Myogenin, and Mhc) and a muscle degradation factor (Murf1). On the other hand, Fam210a siRNA did not affect mRNA encoding the apoptotic factors Bcl-2 and Bax and the extent of apoptosis as measured by ELISA in C2C12 cells. In contrast, Fam210a siRNA increased the mRNA level of Mmp-12, which induces osteoclastogenesis. Interestingly, insulin and 1,25(OH)2D, which are known to affect cell metabolism and muscle function, significantly increased the level of Fam210a mRNA in a dose-dependent manner. In addition, a PI3-kinase inhibitor and reduction in endogenous levels of the vitamin D receptor (VDR) by siRNA suppressed insulin- and 1,25(OH)2D-induced expression of Fam210a, respectively. In conclusion, Fam210a might enhance myoblast differentiation and proteolysis. Moreover, insulin and 1,25(OH)2D may induce myoblast differentiation and degradation by enhancing the expression of Fam210a.