Icariin Facilitates Osteogenic Differentiation and Suppresses Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by Enhancing SOST Methylation in Postmenopausal Osteoporosis

ABSTRACT Purpose Postmenopausal osteoporosis (PMO) is mainly concerned with the imbalance of bone resorption and bone formation. Icariin (ICA) plays a vital role in bone protection. This study investigated the mechanism of ICA in PMO rats. Methods The rats were treated with ovariectomy (OVX) and ICA. Bone structure parameters were measured by Micro‐CT. BMSCs were obtained from normal rats, OVX rats, and ICA‐treated rats. BMSCs were infected with SOST overexpression lentivirus, and TWS119, an activator of Wnt pathway, was introduced for joint experiment. The binding of ERα to SOST promoter was verified. OVX/ICA rats were injected with DNA methyltransferase inhibitor 5‐Aza‐dC. Result ICA increased bone mass and decreased bone marrow fat content in OVX rats. ICA facilitated osteogenic differentiation and repressed adipogenic differentiation of BMSCs. Overexpressing SOST antagonized the effect of ICA, whereas TWS119 rescued the effect of overexpressing SOST. ICA reduced SOST expression by attenuating the effect of ERα. Methylation of SOST inhibited ERα binding to SOST promoter. In vivo experiments confirmed that ICA improved bone mass and reduced bone marrow fat content by enhancing SOST methylation. Conclusion Overall, ICA upregulated SOST methylation and inhibited the binding of ERα to SOST promoter, thereby promoting osteogenic differentiation and repressing adipogenic differentiation of BMSCs.