The Metabolic Landscape in Osteoarthritis

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Wu, Xiaoxin
Fan, Xiwei
Crawford, Ross
Xiao, Yin
Prasadam, Indira
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2022
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Abstract

Articular cartilage function depends on the temporal and zonal distribution of coordinated metabolic regulation in chondrocytes. Emerging evidence shows the importance of cellular metabolism in the molecular control of the cartilage and its dysregulation in degenerative diseases like osteoarthritis (OA). Compared to most other tissues, chondrocytes are sparsely located in the extracellular matrix, lacking the typical proximity of neural, vascular, and lymphatic tissue. Making up under 5% of the total tissue weight of cartilage, chondrocytes have a relative deficiency of access to nutrients and oxygen, as well as limited pathways for metabolite removal. This makes cartilage a unique tissue with hypocellularity, prolonged metabolic rate, and tissue turnover. Studies in the past decade have shown that several pathways of central carbon metabolism are essential for cartilage homeostasis. Here, we summarised the literature findings on the role of cellular metabolism in determining the chondrocyte function and how this metabolic dysregulation led to cartilage aging in OA and provided an outlook on how the field may evolve in the coming years. Although the various energy metabolism pathways are inextricably linked with one another, for the purpose of this review, we initially endeavoured to examine them individually and in relative isolation. Subsequently, we comment on what is known regarding the integration and linked signalling pathways between these systems and the therapeutic opportunities for targeting OA metabolism.

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Aging and Disease

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13

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4

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© 2021 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium provided the original author and source are credited.

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Biomedical engineering

Rheumatology and arthritis

Science & Technology

Life Sciences & Biomedicine

Geriatrics & Gerontology

energy metabolism

osteoarthritis

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Wu, X; Fan, X; Crawford, R; Xiao, Y; Prasadam, I, The Metabolic Landscape in Osteoarthritis, Aging and Disease, 2022, 13 (4), pp. 1166-1182

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