自噬
PI3K/AKT/mTOR通路
成骨细胞
蛋白激酶B
细胞凋亡
糖皮质激素
化学
细胞生物学
内分泌学
内科学
生物
体外
医学
生物化学
作者
Jishang Huang,Yongjun Ye,Yaosheng Xiao,Qun Ren,Qingluo Zhou,Mingliang Zhong,Linhui Jiao,Longhuo Wu
标识
DOI:10.1016/j.biopha.2022.113829
摘要
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.
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