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

iScience (Sep 2024)

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

Journal volume & issue: Vol. 27, no. 9
p. 110597

Abstract

Read online

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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

About the journal

Abstract

Keywords