University of Oulu

Linli Zheng, Ziji Zhang, Puyi Sheng, Ali Mobasheri, The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis, Ageing Research Reviews, Volume 66, 2021, 101249, ISSN 1568-1637,

The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis

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Author: Zheng, Linli1; Zhang, Ziji1; Sheng, Puyi1;
Organizations: 1Department of Joint Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080 China
2Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, PO Box 5000, FI-90014 Oulu, Finland
3Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, LT-08406, Vilnius, Lithuania
4Departments of Orthopedics, Rheumatology and Clinical Immunology, University Medical Center Utrecht, 508 GA, Utrecht, The Netherlands
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 6.5 MB)
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Language: English
Published: Elsevier, 2021
Publish Date: 2021-05-20


Osteoarthritis (OA) is a degenerative joint disease characterized by low-grade inflammation and high levels of clinical heterogeneity. Aberrant chondrocyte metabolism is a response to changes in the inflammatory microenvironment and may play a key role in cartilage degeneration and OA progression. Under conditions of environmental stress, chondrocytes tend to adapt their metabolism to microenvironmental changes by shifting from one metabolic pathway to another, for example from oxidative phosphorylation to glycolysis. Similar changes occur in other joint cells, including synoviocytes. Switching between these pathways is implicated in metabolic alterations that involve mitochondrial dysfunction, enhanced anaerobic glycolysis, and altered lipid and amino acid metabolism. The shift between oxidative phosphorylation and glycolysis is mainly regulated by the AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) pathways. Chondrocyte metabolic changes are likely to be a feature of different OA phenotypes. Determining the role of chondrocyte metabolism in OA has revealed key features of disease pathogenesis. Future research should place greater emphasis on immunometabolism and altered metabolic pathways as a means to understand the pathophysiology of age-related OA. This knowledge will advance the development of new drugs against therapeutic targets of metabolic significance.

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Series: Ageing research reviews
ISSN: 1568-1637
ISSN-E: 1872-9649
ISSN-L: 1568-1637
Volume: 66
Article number: 101249
DOI: 10.1016/j.arr.2020.101249
Type of Publication: A2 Review article in a scientific journal
Field of Science: 1182 Biochemistry, cell and molecular biology
3121 General medicine, internal medicine and other clinical medicine
Funding: This study was supported by the National Natural Science Foundation of China through grants 81874014 and 81672198 awarded to Prof Ziji Zhang and grant 81972050 awarded to Prof Puyi Sheng. Prof Ali Mobasheri has received funding from the following sources: The European Commission Framework 7 programme (EU FP7; HEALTH.2012.2.4.5-2, project number 305815; Novel Diagnostics and Biomarkers for Early Identification of Chronic Inflammatory Joint Diseases). The Innovative Medicines Initiative Joint Undertaking under grant agreement No. 115770, resources of which are composed of financial contribution from the European Union’s Seventh Framework programme (FP7/2007-2013) and EFPIA companies’ in-kind contribution. Prof Ali Mobasheri also acknowledges funding from the European Commission through a Marie Curie Intra-European Fellowship for Career Development grant (project number 625746; acronym: CHONDRION; FP7-PEOPLE-2013-IEF) and financial support from the European Structural and Social Funds (ES Struktūrinės Paramos) through the Research Council of Lithuania (Lietuvos Mokslo Taryba) according to the activity “Improvement of researchers’ qualification by implementing world-class R&D projects” of Measure No. 09.3.3-LMT-K-712 (grant application code: 09.3.3-LMT-K-712-01-0157, agreement No. DOTSUT-215) and the new funding programme: “Attracting Foreign Researchers for Research Implementation (2018-2022)”, Grant No 01.2.2-LMT-K-718-02-0022.
Copyright information: © 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (