SIRT3 alleviates high glucose-induced chondrocyte injury through the promotion of autophagy and suppression of apoptosis in osteoarthritis progression.

ABSTRACT

A growing amount of epidemiological evidence proposes diabetes mellitus (DM) to be an independent risk factor for osteoarthritis (OA). Sirtuin 3 (SIRT3), which is mainly located in mitochondria, belongs to the family of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases and is involved in the physiological and pathological processes of cell regulation. The aim of this study was to investigate the effects of SIRT3 on diabetic OA and underlying mechanisms in the prevention of type 2 DM (T2DM)-induced articular cartilage damage. High-fat and high-sugar diets combined with streptozotocin (STZ) injection were used for establishing an experimental T2DM rat model. The destabilization of medial meniscus (DMM) surgery was applied to induce the rat OA model. Primary rat chondrocytes were cultivated with a concentration of gradient glucose. Treatment with intra-articular injection of SIRT3 overexpression lentivirus was achieved in vivo, and intervention with SIRT3 knockdown was performed using siRNA transfection in vitro. High glucose content was found to activate inflammatory response, facilitate apoptosis, downregulate autophagy, and exacerbate mitochondrial dysfunction in a dose-dependent manner in rat chondrocytes, which can be deteriorated by SIRT3 knockdown. In addition, articular cartilage damage was found to be more severe in T2DM-OA rats than in DMM-induced OA rats, which can be mitigated by the intra-articular injection of SIRT3 overexpression lentivirus. Targeting SIRT3 is a potential therapeutic strategy for the alleviation of diabetic OA.