P-58 - The chondroprotective function of autophagy against acute exogenous oxidative insult in osteoarthritic chondrocytes is impaired

Abstract

It has been reported that oxidative stress (OS) is involved in the pathogenesis of osteoarthritis (OA) and that defective autophagy/mitophagy is accompanying the OA phenotype. In this study, we analyzed the effect of acute exogenous oxidative insult in control and OA chondrocytes. We analyzed the mRNA and protein levels of genes (Atg5, Beclin-1 and LC3) known to be involved in the formation of the autophagosome in control and OA cells treated with sublethal concentrations of hydrogen peroxide (H2O2). Cells were allowed to recover and the same analyses were performed. Under these conditions morphological differences in the mitochondria of control and OA cells were also assessed. Our results showed that the expression of these genes was significantly reduced in OA cells under normal conditions. Furthermore, in control cells mRNA and protein levels of these genes increased as a result of the OS and decreased back to their original levels 24 h after the treatment. On the contrary, their levels remained high in OA cells even after 24 h. Also, a significantly higher number of impaired mitochondria were observed in OA cells as compared to control cells at all time points. These data offer further understanding on the role of autophagy in response to OS in the onset and progression of OA.