Icariin promotes osteoblast differentiation and inhibits adipogenesis of bone marrow stem cells through activation of Wnt/beta-catenin signaling in vivo and in vitro

摘要

Icariin has been proved to promote the bone regeneration and thus have a therapeutic the potential against osteoporosis. However, the role of icariin in the regulation of osteogenesis and aidpogenesis in osteoporosis remains unclear. The present study was designed to investigate the role of in the icariin in osteoblast and adipocyte commitment and differentiation in a osteoporosis mouse model and a primary culture of murine bone marrow stem cells (BMSCs). In vivo, a total of 72 mice were randomly divided into 3 groups: SHAM group (mice without ovariectomy + normal saline), ICA group (ovariectomy + icariin treatment, 25 mg/kg/day), OVX group (ovariectomy + normal saline). At 12 weeks after surgery, murine long bones were harvest for radiographic evaluation and histomorphological analyses. In vitro, BMSCs were harvested and cultured in osteogenic medium. ALP staining and Oil Red O staining were used to detect the differences of osteoblast and adipocyte differentiation between the icariin treated BMSCs (10(-6) mo1/L) and non treated BMSCs. Western blot and quantitative real time PCR (qPCR) were used to examine the mRNA and protein expression levels of osteogenic and adipogenic related genes and the underlying mechanisms. In mice, oral administration of icariin increased the trabecular bone formation and decreased the adipocyte numbers in bone. In vitro, icariin promoted the expression levels of mRNA and protein of osteogenic related genes and inhibits adipogenic related genes during the culture of BMSCs. Icariin also accelerated the accumulation of active beta-catenin in nucleus and upregulated genes regulated by beta-catenin during the osteogenesis. Our results indicated that icariin promotes osteogenesis while inhibiting adipogenesis of BMSCs through the Wnt/beta-catenin signaling pathway.