LncRNA OIP5-AS1 promotes mitophagy to alleviate osteoarthritis by upregulating PPAR-γ to activate the AMPK/Akt/mTOR pathway.

Abstract

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. 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. 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. OIP5-AS1 promotes PPAR-γ expression to activate the AMPK/Akt/mTOR signalling, thereby enhancing mitophagy and alleviating OA progression.