Astragaloside I Stimulates Osteoblast Differentiation Through the Wnt/-catenin Signaling Pathway

Astragaloside I (As-I), one of the main active ingredients in Astragalus membranaceus, is believed to have osteogenic properties, but this hypothesis has not been investigated in detail. In the present work, the As-I-induced osteogenic effects and its underlying mechanism were studied in MC3T3-E1 cells. The results indicated that the cellular levels of ALP and extracellular matrix calcium increased in a dose-dependent manner by As-I. To clarify the mechanisms involved in this process, the effect of As-I on the key osteogenic-related genes was investigated. We found that As-I stimulated the expression of -catenin and Runx2 in MC3T3-E1 cells, which play central roles in the Wnt/-catenin signaling pathway, suggesting that As-I could promote osteoblastic differentiation by regulating the Wnt/-catenin signaling pathway. Moreover, the osteogenic effect of As-I could be inhibited by DKK-1, which is the classical inhibitor of Wnt/-catenin-signaling pathway. Furthermore, As-I also increased BMP-2, BGP and OPG/RANKL expression, which are also activated by Wnt/-catenin signaling pathway. Taken together, our findings show that As-I stimulates osteoblast differentiation through the Wnt/-catenin signaling pathway, which also activates the BMP pathway and RANK pathway, thus highlighting the As-I for pharmaceutical and medicinal applications such as treating bone disease. Copyright (c) 2016 John Wiley & Sons, Ltd.