安普克
PI3K/AKT/mTOR通路
粒体自噬
蛋白激酶B
基因敲除
下调和上调
品脱1
癌症研究
化学
自噬
信号转导
细胞生物学
磷酸化
细胞凋亡
生物
蛋白激酶A
生物化学
基因
作者
Zhilu Sun,Jie Tang,Ting You,Bihong Zhang,Yu Liu,Fei Liu
摘要
ABSTRACT Objectives Osteoarthritis (OA) is the most common chronic joint degenerative disease. Herein, we investigated long non-coding RNA Opa-interacting protein 5-antisense transcript 1’s (OIP5-AS1) in regulating mitophagy during OA. Methods RNA immunoprecipitation and RNA pull-down verified the relationship between molecules. Cell counting kit-8 detected cell viability. Enzyme-linked immunosorbent assay evaluated inflammatory cytokines secretion. Flow cytometry measured the contents of reactive oxygen species (ROS) and calcium. Immunofluorescence staining analysed TOMM20 and LC3B levels. JC-1 staining was adopted to measure mitochondrial membrane potential. The changes of mitophagy were analysed by transmission electron microscopy. Results Lipopolysaccharide (LPS) treatment contributed to the decrease of chondrocyte viability, and calcium level and inhibited mitochondrial membrane potential, while elevating the secretion of inflammatory factors, ROS, and TOMM20 expression. OIP5-AS1 overexpression inhibited LPS-induced chondrocyte injury and activated mitophagy. OIP5-AS1 upregulated the peroxisome proliferator–activated receptor-γ (PPAR-γ) mRNA level to regulate adenosine monophosphate–activated protein kinase (AMPK)/v-akt murine thymoma viral oncogene homolog (Akt)/mammalian target of rapamycin (mTOR) signalling by interacting with FUS. PPAR-γ overexpression alleviated LPS-induced chondrocyte injury by activating AMPK/Akt/mTOR signalling. PPAR-γ knockdown reversed the promotion of OIP5-AS1 upregulation on mitophagy. Conclusions OIP5-AS1 promotes PPAR-γ expression to activate the AMPK/Akt/mTOR signalling, thereby enhancing mitophagy and alleviating OA progression.
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