WITHDRAWN: OPA1 protected against IL-1β-induced chondrocyte dysfunction by alleviating mitochondrial dysfunction and oxidative stress through activation of Parkin-mediated mitophagy

Abstract

Mitophagy affects mitochondrial function and intracellular oxidative stress, and plays essential roles in apoptosis and extracellular matrix (ECM) degradation in osteoarthritis (OA) development. Optic atrophy 1 (OPA1) has been verified to protect cell against damage by inducing mitophagy. However, the function and underlying mechanism of OPA1 in OA remains largely unknown. Here, interleukin (IL)-1β-treated chondrocytes were used to mimic pathological environment of OA progress in vitro. Our results showed that the expression of OPA1 was decreased in cartilage tissue of OA patients and IL-1β-treated chondrocytes. Overexpression of OPA1 inhibited the IL-1β-induced chondrocyte apoptosis and ECM degradation, while OPA1 knockdown significantly exacerbated the effects of IL-1β on chondrocyte apoptosis and ECM degradation. Moreover, OPA1 overexpression enhanced mitochondrial membrane potential, ATP production, the expression of mitochondrial dynamics-related genes and antioxidant enzyme activity, indicating that OPA1 attenuated the IL-1β-induced mitochondrial dysfunction and oxidative stress. Interestingly, the expression of mitophagy-related proteins in IL-1β-induced cells was up-regulated by OPA1 overexpression. Furthermore, Silencing Parkin reversed the activated effect of OPA1 on mitophagy-related proteins, suggesting that Parkin signaling was involved in the mitophagy induced by OPA1. the protective roles of OPA1 in IL-1β-induced mitochondrial dysfunction, oxidative stress, apoptosis and ECM underproduction were suppressed by silencing Parkin. Taken together, OPA1 protected the IL-1β-induced chondrocytes against apoptosis and ECM degradation by alleviating mitochondrial dysfunction and oxidative stress through induction of Parkin-mediated mitophagy. These findings suggest the protective effects of OPA1 in OA.