Geniposide ameliorates glucocorticoid-induced osteoblast apoptosis by activating autophagy

• Published in: Biomedicine & pharmacotherapy Vol. 155; p. 113829
• Main Authors: Huang, Jishang, Ye, Yongjun, Xiao, Yaosheng, Ren, Qun, Zhou, Qingluo, Zhong, Mingliang, Jiao, Linhui, Wu, Longhuo
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.11.2022; Elsevier
• Subjects: Apoptosis; Autophagy; Geniposide; GLP-1R; Osteoblast; PI3K/Akt/mTOR; Osteoblast; Geniposide; Autophagy; PI3K/Akt/mTOR; Apoptosis; GLP-1R
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.113829

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. [Display omitted] •GEN exhibits protective activity against OP.•GEN inhibits DEX-induced osteoblast apoptosis by activating autophagy.•GEN activates autophagy by mediating PI3K/AKT/mTOR pathway.•GEN inhibits apoptosis and activates autophagy in GLP-1R-dependent manner.