Geraniin Promotes Osteoblast Proliferation, Bone Formation, and Autophagy by Regulating the PI3K/Akt/mTOR Cascade to Improve Glucocorticoid-Induced Osteoporosis.

Abstract

Geraniin is a plant natural product that has been testified to perfect osteoporosis (OP). However, Geraniin's impacts on osteoblast autophagy and its latent molecular mechanisms remain uncertain. In this study, Geraniin's impacts on autophagy in osteoblasts were figured out and its molecular mechanism was uncovered. We established in vivo and in vitro models of OP using glucocorticoids and administered Geraniin. The results manifested that Geraniin dose-dependently promoted the phosphorylation of PI3K/Akt/mTOR in OP rats and osteoblasts, increased the bone mineral density, bone surface area/bone volume, Trabecular number and trabecular bone thickness of rat femurs, enhanced alkaline phosphatase activity in OP rats and osteoblasts, elevated osteogenesis-linked proteins RUNX2, OSX and OCN, facilitated autophagosome formation in osteoblasts, elevated Beclin-1 and ACTG5 expression levels and LC3II/LC3I ratio and downregulated p62. However, these effects of Geraniin were attenuated by PI3K/Akt/mTOR inhibitors. All in all, the results of this study indicate Geraniin can perfect glucocorticoid-induced OP by motivating autophagy in osteoblasts through PI3K/Akt/mTOR cascade, which offers strong data support for the future development of Geraniin as a drug for OP cure.