title: Calycosin-7-O-β-d-glucopyranoside stimulates osteoblast differentiation through regulating the BMP/WNT signaling pathways.
abstract: The isoflavone calycosin-7-O-β-d-glucopyranoside (CG) is a principal constituent of Astragalus membranaceus (AR) and has been reported to inhibit osteoclast development in vitro and bone loss in vivo. The aim of this study was to investigate the osteogenic effects of CG and its underlying mechanism in ST2 cells. The results show that exposure of cells to CG in osteogenic differentiation medium increases ALP activity, osteocalcin (Ocal) mRNA expression and the osteoblastic mineralization process. Mechanistically, CG treatment increased the expression of bone morphogenetic protein 2 (BMP-2), p-Smad 1/5/8, β-catenin and Runx2, all of which are regulators of the BMP- or wingless-type MMTV integration site family (WNT)/β-catenin-signaling pathways. Moreover, the osteogenic effects of CG were inhibited by Noggin and DKK-1 which are classical inhibitors of the BMP and WNT/β-catenin-signaling pathways, respectively. Taken together, the results indicate that CG promotes the osteoblastic differentiation of ST2 cells through regulating the BMP/WNT signaling pathways. On this basis, CG may be a useful lead compound for improving the treatment of bone-decreasing diseases and enhancing bone regeneration.
authors.affiliation: Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, Hubei University, Wuhan 430062, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jian
authors.affiliation: Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, Hubei University, Wuhan 430062, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Sun
authors.affiliation: Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, Hubei University, Wuhan 430062, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, Hubei University, Wuhan 430062, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, Hubei University, Wuhan 430062, China.
authors.forename: Jichao
authors.initials: J
authors.lastname: Liang
authors.affiliation: Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, Hubei University, Wuhan 430062, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
keywords: ALP, alkaline phosphatase; AR, Astragalus membranaceus; BMP signaling pathway; BMP, bone morphogenetic protein; CG, calycosin-7-O-β-d-glucopyranoside; Calycosin-7-O-β-d-glucopyranoside; DKK-1, dickkopf-1; ECL, enhanced chemiluminescence; FGF, fibroblast growth factor; HAase, hyaluronidase; IGF1, insulin-like growth factor 1; MAPK, mitogen-activated protein kinase; MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; OBM, osteogenic differentiation medium; OPN, osteopontin; OVX, ovariectomized; Ocal, osteocalcin; Osteoblastic differentiation; PVDF, polyvinylidine fluoride; ST2 cells; TGF-β, transforming growth factor β; WNT, wingless-type MMTV integration site family; WNT/β-catenin signaling pathway