Geniposide ameliorates glucocorticoid-induced osteoblast apoptosis by activating autophagy

Long-term exposure to glucocorticoid (GC) contributes to the development of osteoporosis (OP), which is correlated with the risk of fracture. Pathologically, GC-induced bone loss is associated with osteoblast Apoptosis. Geniposide (GEN), a natural occurring compound derived from Eucommia ulmoides, has been reported to ameliorate dexamethasone (DEX)-induced OP. Our previous study shows that GEN exhibits protective activity against DEX-induced OP by attenuating endoplasmic reticulum stress and decreasing Apoptosis in osteoblasts. However, the molecular mechanisms of GEN in inhibiting DEX-induced osteoblast Apoptosis still need further elucidation. In this article, a molecular target network of GEN against OP was screened. It was found that GEN might interact with OP by mediating PI3K/Akt pathway, which is the upstream factor in regulating Autophagy. GEN exhibited protective activity against DEX-induced Apoptosis by activating Autophagy in vivo and in vitro. Blockage of Autophagy, activation of PI3K/Akt/mTOR pathway, or inhibition of GLP-1R activity could eliminate the protective effects of GEN against DEX-induced Apoptosis. Collectively, GEN ameliorated DEX-induced osteoblast Apoptosis by activating Autophagy through GLP-1R/PI3K/Akt/mTOR pathway.

Apoptosis; Autophagy; GLP-1R; Geniposide; Osteoblast; PI3K/Akt/mTOR.