YK11 promotes osteogenic differentiation of BMSCs and repair of bone defects.

Abstract

The selective androgen receptor modulator (SARM), YK11, promotes the anabolism of muscle cells and osteoblastic precursor cells. Still, its effects on bone marrow-derived mesenchymal stem cells (BMSCs) and the repair of cranial bone defects are unknown. Here, the effects of different concentrations of YK11 on the osteogenic differentiation of BMSCs were determined. Subsequently, AR was inhibited to investigate whether the effect of YK11 on osteogenic differentiation of BMSCs was affected. A model of cranial defects was constructed to investigate the effects of YK11-equipped hydrogel on cranial defect repair as well as the effects of YK11 on cranial defect repair after inhibiting AR. Finally, the possible pathway of YK11 regulating osteogenic differentiation of BMSCs was explored. Our results show 2μM YK11 promoted the proliferation of BMSCs. 0.25-4μM YK11 could promote osteogenesis of BMSCs and the promoting effect was gradually enhanced with the concentration increase. In vivo, 0.5mg/ml YK11 and 1 mg/ml YK11 could promote the repair of cranial bone defects. After inhibiting AR, the effects of YK11 in promoting both osteogenic differentiation of BMSCs and repair of cranial defects were suppressed. YK11 may regulate the osteogenic differentiation of BMSCs through the BMP2/Smad signaling pathway. In conclusion, YK11 promoted the osteogenic differentiation of BMSCs by activation on AR. Meanwhile, YK11 promoted the repair of cranial bone defects in rats in vivo. The BMP2 (bone morphogenetic protein 2)/Smad signaling pathway may be involved in the regulation of osteogenic differentiation of BMSCs by YK11.