Hydrogen sulfide inhibits endoplasmic reticulum stress through the GRP78/mTOR pathway in rat chondrocytes subjected to oxidative stress

The activation of oxidative stress is a primary cause of chondrocyte apoptosis in osteoarthritis (OA). The 78-kDa glucose-regulated protein (GRP78)/mammalian target of rapamycin (mTOR) signaling pathway has been demonstrated to be linked with the endoplasmic reticulum (ER) and autophagy. Hydrogen sulfide (H(2)S) has been reported to exert antioxidant effects. The present study investigated oxidative stress levels via 2′,7′-dichlorofluorescin diacetate and MitoSOX staining, apoptosis rates via flow cytometry and the expression levels of ER stress-related proteins in GYY4137 (donor of H(2)S)-treated chondrocytes (CHs). CHs were isolated from the bilateral hip joints of male rats to examine mitochondrial permeability transition pore opening- and mTOR signaling pathway-related proteins. The results demonstrated that tert-Butyl hydroperoxide (TBHP) increased CH apoptosis, and treatment with GYY4137 ameliorated TBHP-mediated the generation of ROS and CH apoptosis. Moreover, TBHP-treated CHs displayed elevated ER stress sensor expression levels and apoptotic rates; however, the TBHP-induced protein expression levels were decreased following GYY4137 treatment. In the present study, treatment with either GYY4137 or transfection with GRP78 siRNA both suppressed the activation of p-P70S6k and p-mTOR. H(2)S played an important role in regulating ER stress in TBHP-stimulated CHs. GYY4137 promoted autophagy, which was accompanied by the inhibition of ER stress. On the whole, the present study demonstrates that TBHP-induced oxidative stress stimulates ER interactions and CH apoptosis, which are suppressed by exogenous H(2)S via modulating the GRP78/mTOR signaling pathway.