Effect and mechanism of psoralidin on promoting osteogenesis and inhibiting adipogenesis.

Affiliation

Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518057, China; Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: [Email]

Abstract

BACKGROUND : Psoralidin (PL), a prenylated coumestrol, is isolated from Psoralea corylifolia L. (Fabaceae), which is frequently used for treatment of osteoporosis.
OBJECTIVE : This study was designed to investigate the dual effects and potential mechanism of PL on promoting osteogenesis and inhibiting adipogenesis.
METHODS : Bone marrow mesenchymal stem cells (BMSCs) were used to investigate the effect of PL on stimulating osteogenesis and inhibiting adipogenesis, while preosteoblast MC3T3-E1 cells and preadipocyte 3T3-L1 cells were employed to explore the potential mechanisms. Estradiol (E2) and ICI 182,780 (ICI) were used as the specific agonist and antagonist of classical estrogen receptors (ER), respectively, to interfere with classical ER signaling. Meanwhile, G-1 and G-15 were introduced as the selective agonist and antagonist of G protein coupled receptor 30 (GRP30, a membrane ER) to further clarify if membrane ER involved in PL mediating osteogenesis and adipogenesis RESULTS: PL not only promoted mineralization, but also inhibited adipocytes formation of BMSCs. In terms of osteogenesis, PL enhanced calcium nodule formation, alkaline phosphatase activity and osteocalcin levels in MC3T3-E1 cells. As for adipogenesis, PL decreased adipocyte formation in 3T3-L1 cells through down-regulating several mRNA expressions and protein synthesis of adipogenesis related factors. ICI completely blocked the effect of PL in promoting osteogenesis, but only partially suppressed its effect in inhibition of adipogenesis, while G-15 partially suppressed the effect of PL on promoting mineralization and inhibiting oil drop formation. Furthermore, during suppression of adipocyte differentiation, PL regulated protein kinase B / glycogen synthase kinase 3β / β-catenin signaling pathway.
CONCLUSIONS : PL promoted osteogenesis via mediating classical ER pathway, and inhibited adipocytes formation by regulating combined classical and membrane ER pathways. PL might be a potential candidate for the treatment of postmenopausal osteoporosis by modulating the competitive relationship between osteogenesis and adipogenesis of bone marrow mesenchymal stem cells.

Keywords

Adipogenesis,Estrogen receptor (ER),GRP30 receptor,Osteogenesis,Psoralidin (PL),

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