Zuogui Wan modulates macrophage polarization and promotes osteogenic differentiation through regulation of CD51-positive bone marrow mesenchymal stem cells

Abstract Background Zuogui Wan (ZGW) is a traditional herbal formula used to treat chronic kidney and bone diseases. Previous research has shown that ZGW slows down the aging process of bone marrow mesenchymal stem cells (BMSCs) and improves bone metabolism. However, its role in treating postmenopausal osteoporosis (PMOP) has not yet been fully investigated. Therefore, we investigated the therapeutic effects of ZGW and its potential mechanisms in an ovariectomy (OVX)-induced osteoporosis rat model. Results We observed significant improvements in bone loss and the osteoporotic phenotype in OVX rats treated with ZGW. These findings were confirmed with micro-computed tomography (micro-CT) and histomorphological analysis. We also discovered that ZGW reversed the macrophage imbalance, which in turn inhibited osteoclast differentiation and bone resorption. Furthermore, RNA-Seq results revealed the active expression of CD51 in BMSCs before and after ZGW therapy, which is associated with macrophage polarization and osteoblastic differentiation. The results also showed that ZGW decreased CD51 + BMSCs levels, which is closely related to the inhibition of osteoblast differentiation and promotion of osteoclast resorption. Conclusions Our study demonstrated that ZGW may improve postmenopausal osteoporosis by restoring macrophage polarization and down-regulating CD51 + BMSCs. In addition, ZGW promoted osteoblast formation and inhibited osteoclast resorption.