Salidroside (SAL) is one of main active components of Rhodiola rosea L and possesses diverse pharmacological effects. However, the direct role of SAL in bone metabolism remains elusive. In this study, effects of SAL on osteoblast differentiation of murine pluripotent mesenchymal cell line C3H10T1/2 and osteoblastic cell line MC3T3-E1 were examined. We first identified SAL as a potential BMP2 activator in a cell-based screening assay. SAL (0.5-10 mu M) could slightly promote the proliferation and greatly increase the alkaline phosphatase (ALP) activity in both cells. Furthermore, SAL increased the mRNA expressions of osteoblast marker genes in either C3H10T1/2 or MC3T3-E1 cells after treatment for different time. Moreover, the mineralization of C3H10T1/2 cells assayed by Alizarin red S staining was dose-dependently increased by SAL Mechanistically, SAL increased the mRNA level of genes involved in the regulation of BMP signaling pathway, including BMP2, BMP6 and BMP7 and enhanced the phosphorylation of Smad1/5/8 and ERK1/2. The osteogenic effect of SAL was abolished by BMP antagonist noggin or by BMP receptor kinase inhibitor dorsomorphin. Further in vivo study demonstrated that SAL reversed bone loss in ovariectomized rats. Collectively, our findings indicate that SAL regulates bone metabolism through BMP signaling pathway. (C) 2013 Elsevier Ltd. All rights reserved.