Trehalose ameliorates oxidative stress-mediated mitochondrial dysfunction and ER stress via selective autophagy stimulation and autophagic flux restoration in osteoarthritis development

摘要: Oxidative stress-related apoptosis and autophagy play crucial roles in the development of osteoarthritis (OA), a progressive cartilage degenerative disease with multifactorial etiologies. Here, we determined autophagic flux changes human OA tert-Butyl hydroperoxide (TBHP)-treated chondrocytes. In addition, explored potential protective effects trehalose, novel Mammalian Target Rapamycin (mTOR)-independent inducer, TBHP-treated mouse chondrocytes destabilized medial meniscus (DMM) model. We found aberrant p62 accumulation increased Consistently, cleaved caspase-3 levels under oxidative stress. Furthermore, trehalose restored stress-induced disruption targeted selectively by activating BCL2 interacting protein 3 (BNIP3) Phosphoglycerate mutase family member 5 (PGAM5). Trehalose could ameliorate stress-mediated mitochondrial membrane collapse, ATP level decrease, dynamin-related 1 (drp-1) translocation into mitochondria, upregulation proteins involved mitochondria endoplasmic reticulum (ER) pathway. suppressed cleavage caspase poly(ADP-ribose) polymerase (PARP) prevented DNA damage However, anti-apoptotic were partially abolished inhibitor chloroquine BNIP3- siRNA. The effect was also Taken together, these results indicate that has through suppression injury ER stress which is dependent on promotion induction selective autophagy. Thus, promising therapeutic agent for OA.