Leptin attenuates the osteogenic induction potential of BMP9 by increasing β-catenin malonylation modification via Sirt5 down-regulation

瘦素通过下调 Sirt5 增加 β-catenin 丙二酰化修饰来减弱 BMP9 的成骨诱导潜力

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作者:Kai-Xin Ke, Xiang Gao, Lu Liu, Wen-Ge He, Yue Jiang, Cheng-Bin Long, Gan Zhong, Zheng-Hao Xu, Zhong-Liang Deng, Bai-Cheng He, Ning Hu

Abstract

BMP9 has demonstrated significant osteogenic potential. In this study, we investigated the effect of Leptin on BMP9-induced osteogenic differentiation. Firstly, we found Leptin was decreased during BMP9-induced osteogenic differentiation and serum Leptin concentrations were increased in the ovariectomized (OVX) rats. Both in vitro and in vivo, exogenous expression of Leptin inhibited the process of osteogenic differentiation, whereas silencing Leptin enhanced. Exogenous Leptin could increase the malonylation of β-catenin. However, BMP9 could increase the level of Sirt5 and subsequently decrease the malonylation of β-catenin; the BMP9-induced osteogenic differentiation was inhibited by silencing Sirt5. These data suggested that Leptin can inhibit the BMP9-induced osteogenic differentiation, which may be mediated through reducing the activity of Wnt/β-catenin signalling via down-regulating Sirt5 to increase the malonylation level of β-catenin partly.

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