Osteoarthritis as an evolutionary legacy: Biological ageing and chondrocyte hypertrophy

Objective: Osteoarthritis (OA) is a progressive joint disease habitually linked to ageing, characterized by the gradual breakdown of cartilage leading to pain and reduced mobility. Historically viewed as mainly a “wear and tear” condition, new insights suggest that OA may be part of an evolutionary,...

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Main Author: Peter M. van der Kraan
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Osteoarthritis and Cartilage Open
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2665913125000603
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author Peter M. van der Kraan
author_facet Peter M. van der Kraan
author_sort Peter M. van der Kraan
collection DOAJ
description Objective: Osteoarthritis (OA) is a progressive joint disease habitually linked to ageing, characterized by the gradual breakdown of cartilage leading to pain and reduced mobility. Historically viewed as mainly a “wear and tear” condition, new insights suggest that OA may be part of an evolutionary, age-related biological process rather than mainly driven by mechanical damage. Design: This conceptual paper discusses the model of antagonistic pleiotropy that proposes that certain genes beneficial early in life may contribute to diseases in the context of OA. Results: Findings indicate that OA is connected to biological and not to chronological age supporting the idea that OA is not merely a wear and tear process. Chondrocyte hypertrophy, essential in endochondral bone formation at a (pre)reproductive age, is stimulated by a displaced and wrongly timed endochondral ossification quasi-program in age-related OA. Age-related chondrocyte hypertrophic differentiation in articular cartilage is likely driven by loss of loading-induced TGF-β signaling. Conclusion: Comprehending OA within this evolutionary and biological frame provides a solid alternative to the theory of “wear and tear”, offering insights into further understanding, prevention and disease management.
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spelling doaj-art-00fe7cd2436f40aaa0bbb49cb4d9f78b2025-08-20T03:47:36ZengElsevierOsteoarthritis and Cartilage Open2665-91312025-09-017310062410.1016/j.ocarto.2025.100624Osteoarthritis as an evolutionary legacy: Biological ageing and chondrocyte hypertrophyPeter M. van der Kraan0Radboudumc, Rheumatology, Experimental Rheumatology, PO Box 9101, 6500 HB Nijmegen, the NetherlandsObjective: Osteoarthritis (OA) is a progressive joint disease habitually linked to ageing, characterized by the gradual breakdown of cartilage leading to pain and reduced mobility. Historically viewed as mainly a “wear and tear” condition, new insights suggest that OA may be part of an evolutionary, age-related biological process rather than mainly driven by mechanical damage. Design: This conceptual paper discusses the model of antagonistic pleiotropy that proposes that certain genes beneficial early in life may contribute to diseases in the context of OA. Results: Findings indicate that OA is connected to biological and not to chronological age supporting the idea that OA is not merely a wear and tear process. Chondrocyte hypertrophy, essential in endochondral bone formation at a (pre)reproductive age, is stimulated by a displaced and wrongly timed endochondral ossification quasi-program in age-related OA. Age-related chondrocyte hypertrophic differentiation in articular cartilage is likely driven by loss of loading-induced TGF-β signaling. Conclusion: Comprehending OA within this evolutionary and biological frame provides a solid alternative to the theory of “wear and tear”, offering insights into further understanding, prevention and disease management.http://www.sciencedirect.com/science/article/pii/S2665913125000603OsteoarthritisEndochondral ossificationChondrocyte hypertrophyAgeingEvolution
spellingShingle Peter M. van der Kraan
Osteoarthritis as an evolutionary legacy: Biological ageing and chondrocyte hypertrophy
Osteoarthritis and Cartilage Open
Osteoarthritis
Endochondral ossification
Chondrocyte hypertrophy
Ageing
Evolution
title Osteoarthritis as an evolutionary legacy: Biological ageing and chondrocyte hypertrophy
title_full Osteoarthritis as an evolutionary legacy: Biological ageing and chondrocyte hypertrophy
title_fullStr Osteoarthritis as an evolutionary legacy: Biological ageing and chondrocyte hypertrophy
title_full_unstemmed Osteoarthritis as an evolutionary legacy: Biological ageing and chondrocyte hypertrophy
title_short Osteoarthritis as an evolutionary legacy: Biological ageing and chondrocyte hypertrophy
title_sort osteoarthritis as an evolutionary legacy biological ageing and chondrocyte hypertrophy
topic Osteoarthritis
Endochondral ossification
Chondrocyte hypertrophy
Ageing
Evolution
url http://www.sciencedirect.com/science/article/pii/S2665913125000603
work_keys_str_mv AT petermvanderkraan osteoarthritisasanevolutionarylegacybiologicalageingandchondrocytehypertrophy