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

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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)

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.

Suggested Citation

  • Sujeong Park & In-Jeoung Baek & Ji Hyun Ryu & Churl-Hong Chun & Eun-Jung Jin, 2022. "PPARα−ACOT12 axis is responsible for maintaining cartilage homeostasis through modulating de novo lipogenesis," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27738-y
    DOI: 10.1038/s41467-021-27738-y
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