Cartilage loss is a central event in the pathogenesis of osteoarthritis (OA), though other than mechanical loading, the biochemical mechanisms underlying OA pathology remain poorly elucidated. We investigated the role of Pink1-mediated mitophagy in mitochondrial fission, a crucial process in OA pathogenesis. We used a monosodium iodoacetate (MIA)-induced rodent model of OA, which inhibits the activity of articular chondrocytes, leading to disruption of glycolytic energy metabolism and eventual cell death. The OA rat cartilage exhibits significant induction of autophagy-related proteins LC3B and p62, similar to human osteoarthritic cartilage. Moreover, expression of Pink1 and Parkin proteins were also increased in OA. Here, we confirm that Pink1-mediated mitophagy leads to cell death in chondrocytes following MIA treatment, while deficiency in Pink1 expression was associated with decreased cartilage damage and pain behaviors in MIA-induced OA. Finally, we found that autophagy and mitophagy-related genes are highly expressed in human osteoarthritic cartilage. These results indicate that OA is a degenerative condition associated with mitophagy, and suggest that targeting the Pink1 pathway may provide a therapeutic avenue for OA treatment.
Keywords: MIA (monosodium iodoacetate); Pink1; mitochondrial dynamics; mitophagy; osteoarthritis.