| Objective To investigate the protective effect of astragalus polysaccharide on glucocorticoid-induced osteoporosis (GIOP) through the PI3K/AKT/mTOR signaling pathway in vivo and in vitro. Methods Osteoblasts from the differentiated bone marrow mesenchymal stem cells (BM-MSCs) were cultured and were grouped as follows: the PBS group, the model group, the LY294002 group, the astragalus polysaccharide group, and the LY294002+astragalus polysaccharide intervention group. Cell proliferation and differentiation were detected with cell counting kit-8 (CCK8) assay and alkaline phosphatase (ALP) staining, respectively. The formation of autophagosome was observed with Monodansylcadaverine (MDC) staining. Expressions of signaling pathway and autophagy related factors such as Beclin-1 and p62 were detected with Western blotting. Then, the rats were grouped as the normal group, the model group, the LY294002 group, the astragalus polysaccharide group, and the LY294002+astragalus polysaccharide group. Bone mineral density and bone histomorphometry parameters of rats in each group were compared. In addition, the expressions of pathway and autophagy related factors in the cartilage tissue of rats in each groups were also detected. Results The proliferation and differentiation abilities of osteoblasts increased with an increasing concentration of astragalus polysaccharide in a dose-dependent manner. Compared to those in the model group, the expression of PI3K/AKT/mTOR pathway related phosphorylated proteins, the proliferation and differentiation abilities of osteoblasts, the expression of autophagosome and autophagy related factors increased in the astragalus polysaccharide group, but contrary results were found in the LY294002 group (all P<0.05). In vivo, GIOP rats had improved bone mineral density and bone morphology parameters, and elevated expressions of autophagy related factors in the cartilage tissue compared to rats in the model group through astragalus polysaccharide intervention. LY294002 intervention showed the opposite effects (all P<0.05). Moreover, LY294002 partially reversed the effects of astragalus polysaccharide on osteogenic differentiation and bone morphological parameters in GIOP. Conclusion Astragalus polysaccharide exerts protective effect on GIOP through the PI3K/AKT/mTOR pathway, which may be related to autophagy induction and enhanced proliferation of osteoblasts. |