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

Sujeong Park, In-Jeoung Baek, Ji Hyun Ryu, Churl-Hong Chun and Eun-Jung Jin ()
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Sujeong Park: Wonkwang University
In-Jeoung Baek: University of Ulsan College of Medicine
Ji Hyun Ryu: Wonkwang University
Churl-Hong Chun: Wonkwang University School of Medicine
Eun-Jung Jin: Wonkwang University

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-021-27738-y

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