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10-hydroxy-2-decenoic acid prevents osteoarthritis by targeting aspartyl β hydroxylase and inhibiting chondrocyte senescence in male mice preclinically
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10-hydroxy-2-decenoic acid prevents osteoarthritis by targeting aspartyl β hydroxylase and inhibiting chondrocyte senescence in male mice preclinically
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Journal Article
10-hydroxy-2-decenoic acid prevents osteoarthritis by targeting aspartyl β hydroxylase and inhibiting chondrocyte senescence in male mice preclinically
2024
Overview
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.
Chondrocyte senescence is known to play a role in the occurrence and progression of osteoarthritis. Here, the authors demonstrate that 10-hydroxy-2-decenoic acid (10-HDA), a small molecule derived from the food nutrient royal jelly, can prevent osteoarthritis by delaying chondrocyte senescence through targeting aspartyl β-hydroxylase.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14
/ 38
/ 42
/ 49
/ 59
/ 64
/ 64/60
/ 692/4017
/ 96
/ Acids
/ Animals
/ Cartilage, Articular - drug effects
/ Cartilage, Articular - metabolism
/ Cartilage, Articular - pathology
/ Cellular Senescence - drug effects
/ Explants
/ Fatty Acids, Monounsaturated - pharmacology
/ Female
/ Fibrosis
/ Humanities and Social Sciences
/ Humans
/ Male
/ Males
/ Meniscus
/ Mice
/ Osteoarthritis - drug therapy
/ Osteoarthritis - prevention & control
/ Pain
/ Science
