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iScience

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Targeting Parkin-regulated metabolomic change in cartilage in the treatment of osteoarthritis.

Published:27 July 2024 DOI:
Yiyang Ma , Yidan Pang , Ruomu Cao , Zhikai Zheng , Kaiwen Zheng , Yucheng Tian , Xiaoyuan Peng , Delin Liu , Dajiang Du , Lin Du , Zhigang Zhong , Lufeng Yao , Changqing Zhang , Junjie Gao

Abstract

Articular cartilage degeneration may lead to osteoarthritis (OA) during the aging process, but its underlying mechanism remains unknown. Here, we found that chondrocytes exhibited an energy metabolism shift from glycolysis to oxidative phosphorylation (OXPHOS) during aging. Parkin regulates various cellular metabolic processes. Reprogrammed cartilage metabolism by Parkin ablation decreased OXPHOS and increased glycolysis, with ameliorated aging-related OA. Metabolomics analysis indicated that lauroyl-L-carnitine (LLC) was decreased in aged cartilage, but increased in Parkin-deficient cartilage. In?vitro, LLC improved the cartilage matrix synthesis of aged chondrocytes. In?vivo, intra-articular injection of LLC in mice with anterior cruciate ligament transaction (ACLT) ameliorated OA progression. These results suggest that metabolic changes are regulated by Parkin-impaired cartilage during aging, and targeting this metabolomic changes by supplementation with LLC is a promising treatment strategy for ameliorating OA.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
2-(N-(7-NITROBENZ-2-OXA-1,3-DIAZOL-4-YL)AMINO)-2-DEOXYGLUCOSE 186689-07-6 C12H14N4O8 196 suppliers $28.00-$5062.60
2-(N-(7-NITROBENZ-2-OXA-1,3-DIAZOL-4-YL)AMINO)-2-DEOXYGLUCOSE 186689-07-6 C12H14N4O8 196 suppliers $28.00-$5062.60
2-(N-(7-NITROBENZ-2-OXA-1,3-DIAZOL-4-YL)AMINO)-2-DEOXYGLUCOSE 186689-07-6 C12H14N4O8 196 suppliers $28.00-$5062.60
2-(N-(7-NITROBENZ-2-OXA-1,3-DIAZOL-4-YL)AMINO)-2-DEOXYGLUCOSE 186689-07-6 C12H14N4O8 196 suppliers $28.00-$5062.60

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