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

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 and , 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.