Inokosterone activates the BMP2 to promote the osteogenic differentiation of bone marrow mesenchymal stem cells and improve bone loss in ovariectomized rats

Abstract

Evidence suggests that enhancing the osteogenic ability of bone marrow-derived mesenchymal stem cells (BMSCs) may be beneficial in the fight against osteoporosis (OP) effects. Inokosterone (IS) is a major active constituent of Achyranthis bidentatae radix (ABR), which stimulates osteogenic differentiation of mouse embryonic osteoblasts. This study aims to investigate effect of IS on OP using osteogenic differentiated BMSCs and ovariectomy (OVX)-induced OP rats. The BMSCs were treated with 50, 100, or 200 mg/L IS and OP rats were given 2 or 4 mg/kg of IS by gavage. Cell viability, the osteogenic differentiation marker protein expression level, and mineralization were observed. This study proved that IS improved cell viability, osteogenic differentiation, and cellular mineralization in BMSCs and raised expression levels of bone morphogenetic protein-2 (BMP2), Smad1, runt-related transcription factor 2 (RUNX2), collagen I, ALP, and OCN. By BMP2 knockdown/overexpression, this study also proved the BMP2 signaling pathway activation is a potential biological mechanism of IS to improve osteogenic differentiation and mineralization in osteogenic differentiated BMSCs. In OVX-induced OP rats, IS was observed to antagonize bone loss, improve osteogenic differentiation marker protein expression levels, and activate BMP-2, smad1, and RUNX2. These findings provide scientific support for further investigation of the biological mechanisms of IS in ameliorating OP.

Keywords: Bone marrow-derived mesenchymal stem cells; Bone morphogenetic protein-2; Inokosterone; Osteogenic differentiation; Osteoporosis; Ovariectomy.