| First Author | Park S | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 3 |
| PubMed ID | 34987154 | Mgi Jnum | J:335865 |
| Mgi Id | MGI:6857219 | Doi | 10.1038/s41467-021-27738-y |
| Citation | Park S, et al. (2022) PPARalpha-ACOT12 axis is responsible for maintaining cartilage homeostasis through modulating de novo lipogenesis. Nat Commun 13(1):3 |
| abstractText | 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. |
