2. Academic Validation
  3. Targeting Parkin-regulated metabolomic change in cartilage in the treatment of osteoarthritis

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

  • iScience. 2024 Jul 27;27(9):110597. doi: 10.1016/j.isci.2024.110597.
Yiyang Ma 1 2,  Yidan Pang 1 2,  Ruomu Cao 3,  Zhikai Zheng 1 2,  Kaiwen Zheng 1 2,  Yucheng Tian 1 2,  Xiaoyuan Peng 1,  Delin Liu 1 2,  Dajiang Du 1,  Lin Du 4 5,  Zhigang Zhong 4 5,  Lufeng Yao 6,  Changqing Zhang 1 2,  Junjie Gao 1 2
Affiliations

Affiliations

  • 1 Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
  • 2 Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
  • 3 Department of Bone and Joint Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, China.
  • 4 Orthopedics Department, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China.
  • 5 Sports Medicine Institute, Shantou University Medical College, Shantou 515041, China.
  • 6 Department of Orthopaedic Surgery, Ningbo No.6 Hospital, No.1059 East Zhongshan Road, Yinzhou District, Ningbo, Zhejiang 315040, China.
PMID: 39220257 DOI: 10.1016/j.isci.2024.110597
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.

Keywords

Biological sciences; Metabolomics; Molecular biology; Transcriptomics.

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