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; Lin Du; Zhigang Zhong; Lufeng Yao; Changqing Zhang; Jun jie Gao

doi:10.1016/j.isci.2024.110597

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
, Lin Du
, Zhigang Zhong
, Lufeng Yao
, Changqing Zhang
, Jun jie Gao

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

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.

Original language	English
Article number	110597
Number of pages	17
Journal	Iscience
Volume	27
Issue number	9
DOIs	https://doi.org/10.1016/j.isci.2024.110597
Publication status	Published - 20 Sept 2024
Externally published	Yes

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title = "Targeting Parkin-regulated metabolomic change in cartilage in the treatment of osteoarthritis",

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.",

author = "Yiyang Ma and Yidan Pang and Ruomu Cao and Zhikai Zheng and Kaiwen Zheng and Yucheng Tian and Xiaoyuan Peng and Delin Liu and Lin Du and Zhigang Zhong and Lufeng Yao and Changqing Zhang and Gao, \{Jun jie\}",

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doi = "10.1016/j.isci.2024.110597",

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T1 - Targeting Parkin-regulated metabolomic change in cartilage in the treatment of osteoarthritis

AU - Ma, Yiyang

AU - Pang, Yidan

AU - Cao, Ruomu

AU - Zheng, Zhikai

AU - Zheng, Kaiwen

AU - Tian, Yucheng

AU - Peng, Xiaoyuan

AU - Liu, Delin

AU - Du, Lin

AU - Zhong, Zhigang

AU - Yao, Lufeng

AU - Zhang, Changqing

AU - Gao, Jun jie

PY - 2024/9/20

Y1 - 2024/9/20

N2 - 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.

AB - 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.

U2 - 10.1016/j.isci.2024.110597

DO - 10.1016/j.isci.2024.110597

M3 - Article

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SN - 2589-0042

VL - 27

JO - Iscience

JF - Iscience

IS - 9

M1 - 110597

ER -

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

Abstract

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