10-hydroxy-2-decenoic acid prevents osteoarthritis by targeting aspartyl β hydroxylase and inhibiting chondrocyte senescence in male mice preclinically

Nana Geng, Mengtian Fan, Biao Kuang, Fengmei Zhang, Menglin Xian, Lin Deng, Cheng Chen, Yiming Pan, Jianqiang Chen, Naibo Feng, Li Liang, Yuanlan Ye, Kaiwen Liu, Xiaoli Li, Yu Du and Fengjin Guo ()
Additional contact information
Nana Geng: Chongqing Medical University
Mengtian Fan: Chongqing Medical University
Biao Kuang: The Second Affiliated Hospital of Chongqing Medical University
Fengmei Zhang: Chongqing Medical University
Menglin Xian: Chongqing Medical University
Lin Deng: Chongqing Medical University
Cheng Chen: The First Affiliated Hospital of Chongqing Medical University
Yiming Pan: Chongqing Medical University
Jianqiang Chen: Chongqing Medical University
Naibo Feng: Chongqing Medical University
Li Liang: Chongqing Medical University
Yuanlan Ye: Chongqing Medical University
Kaiwen Liu: Chongqing Medical University
Xiaoli Li: Chongqing Medical University
Yu Du: The Second Affiliated Hospital of Chongqing Medical University
Fengjin Guo: Chongqing Medical University

Nature Communications, 2024, vol. 15, issue 1, 1-23

Abstract: Abstract Osteoarthritis is a degenerative joint disease with joint pain as the main symptom, caused by fibrosis and loss of articular cartilage. Due to the complexity and heterogeneity of osteoarthritis, there is a lack of effective individualized disease-modifying osteoarthritis drugs in clinical practice. Chondrocyte senescence is reported to participate in occurrence and progression of osteoarthritis. Here we show that small molecule 10-hydroxy-2-decenoic acid suppresses cartilage degeneration and relieves pain in the chondrocytes, cartilage explants from osteoarthritis patients, surgery-induced medial meniscus destabilization or naturally aged male mice. We further confirm that 10-hydroxy-2-decenoic acid exerts a protective effect by targeting the glycosylation site in the Asp_Arg_Hydrox domain of aspartyl β-hydroxylase. Mechanistically, 10-hydroxy-2-decenoic acid alleviate cellular senescence through the ERK/p53/p21 and GSK3β/p16 pathways in the chondrocytes. Our study uncovers that 10-hydroxy-2-decenoic acid modulate cartilage metabolism by targeting aspartyl β-hydroxylase to inhibit chondrocyte senescence in osteoarthritis. 10-hydroxy-2-decenoic acid may be a promising therapeutic drug against osteoarthritis.

Date: 2024
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DOI: 10.1038/s41467-024-51746-3

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