Yes-associated protein regulates the differentiation and osteoporosis of bone marrow mesenchymal stem cells

Abstract

Mammalian Yes-associated protein (YAP) is involved in the regulation of various biological behaviors. Osteoporosis (OP) is a common orthopedic disease. However, the role of YAP in the differentiation and osteoporosis of Bone marrow mesenchymal stem cells (BMSCs) is unclear. Ovariectomy (OVX)-induced OP rat model was constructed and YAP plasmid was transfected to detect bone density and alkaline phosphatase (ALP) activity. Rat BMSCs were assigned into 3 groups: sham group, OP group, and YAP group, in which YAP plasmid was transfected followed by analysis of YAP expression by real-time PCR. After 14 days of induction culture, type I collagen, Osterix and FABP4 mRNA expression was detected by real-time PCR along with Wnt5 protein expression by western blot and TGF-β secretion by ELISA. In OP rats, YAP expression was significantly down-regulated and the bone density and ALP activity decreased (P <0.05). YAP transfection in OP rats reversed the changes in OP rats. In OP group, YAP expression was decreased, and type I collagen and Osterix expression decreased, FABP4 expression increased, β-catenin expression and TGF-β secretion decreased (P <0.05). Transfection of YAP plasmid in BMSCs of OP group significantly reversed the above changes (P <0.05). In conclusion, YAP level decreases in OP and up-regulating its expression in BMSCs can promote osteogenic differentiation and inhibit adipogenic differentiation by regulating Tnt5/TGF-β signaling.