Sal B targets TAZ to facilitate osteogenesis and reduce adipogenesis through MEK-ERK pathway

Abstract

Salvianolic acid B (Sal B), a major bioactive component of Chinese herb, was identified as a mediator for bone metabolism recently. The aim of this study is to investigate the underlying mechanisms by which Sal B regulates osteogenesis and adipogenesis. We used MC3T3-E1 and 3T3-L1 as the study model to explore the changes of cell differentiation induced by Sal B. The results indicated that Sal B at different concentrations had no obvious toxicity effects on cell proliferation during differentiation. Furthermore, Sal B facilitated osteogenesis but inhibited adipogenesis by increasing the expression of transcriptional co-activator with PDZ-binding motif (TAZ). Accordingly, TAZ knock-down offset the effects of Sal B on cell differentiation into osteoblasts or adipocytes. Notably, the Sal B induced up-expression of TAZ was blocked by U0126 (the MEK-ERK inhibitor), rather than LY294002 (the PI3K-Akt inhibitor). Moreover, Sal B increased the p-ERK/ERK ratio to regulate the TAZ expression as well as the cell differentiation. In summary, this study suggests for the first time that Sal B targets TAZ to facilitate osteogenesis and reduce adipogenesis by activating MEK-ERK signalling pathway, which provides evidence for Sal B to be used as a potential therapeutic agent for the management of bone diseases.