PPARα−ACOT12 axis is responsible for maintaining cartilage homeostasis through modulating de novo lipogenesis

Abstract

Here, in Ppara−/− mice, we found that an increased DNL stimulated the cartilage degradation and identified ACOT12 as a key regulatory factor. Suppressed level of ACOT12 was observed in cartilages of OA patient and OA-induced animal. To determine the role and association of ACOT12 in the OA pathogenesis, we generated Acot12 knockout (KO) (Acot12−/−) mice using RNA-guided endonuclease. Acot12−/− mice displayed the severe cartilage degradation with the stimulation of matrix MMPs and chondrocyte apoptosis through the accumulation of acetyl CoA. Delivery of acetyl CoA-conjugated chitosan complex into cartilage stimulated DNL and cartilage degradation. Moreover, restoration of ACOT12 into human OA chondrocytes and OA-induced mouse cartilage effectively rescued the pathophysiological features of OA by regulating DNL. Taken together, our study suggested ACOT12 as a novel regulatory factor in maintaining cartilage homeostasis and targeting ACOT12 could contribute to developing a new therapeutic strategy for OA.

Touchable Electrochemical Hydrogel Sensor for Detection of Reactive Oxygen Species‐induced Cellular Senescence in Articular Chondrocytes

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TRPM7 channel inhibition attenuates rheumatoid arthritis articular chondrocyte ferroptosis by suppression of the PKCα-NOX4 axis

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The Role of Regulated Programmed Cell Death in Osteoarthritis: From Pathogenesis to Therapy

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