Targeting Parkin-regulated metabolomic change in cartilage in the treatment of osteoarthritis
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
Affiliations
Yiyang Ma
Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; 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
Yidan Pang
Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; 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
Ruomu Cao
Department of Bone and Joint Surgery, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shanxi 710004, China
Zhikai Zheng
Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; 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
Kaiwen Zheng
Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; 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
Yucheng Tian
Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; 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
Xiaoyuan Peng
Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
Delin Liu
Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; 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
Dajiang Du
Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
Lin Du
Orthopedics Department, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China; Sports Medicine Institute, Shantou University Medical College, Shantou 515041, China
Zhigang Zhong
Orthopedics Department, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China; Sports Medicine Institute, Shantou University Medical College, Shantou 515041, China
Lufeng Yao
Department of Orthopaedic Surgery, Ningbo No.6 Hospital, No.1059 East Zhongshan Road, Yinzhou District, Ningbo, Zhejiang 315040, China; Corresponding author
Changqing Zhang
Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; 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; Corresponding author
Junjie Gao
Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; 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; Corresponding author
Summary: 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.
