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 th

SUBMITTER: Park S 

PROVIDER: S-EPMC8733009 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature