Osteoarthritis as an evolutionary legacy: Biological ageing and chondrocyte hypertrophy

Abstract

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.

Keywords: Ageing; Chondrocyte hypertrophy; Endochondral ossification; Evolution; Osteoarthritis.

Fig. 1

Antagonist pleiotropy of the endochondral ossification (quasi)-program. Antagonistic pleiotropy is the concept that genes and processes that enhance fitness early but reduce it later life can still be favoured by natural selection. Even genes that are deleterious in late life can be positively selected for and maintained in the population when having an advantage at the reproductive age.

Fig. 2

The endochondral ossification program and the endochondral ossification quasi-program. Both the endochondral ossification program and the endochondral ossification quasi-program lead to cartilage matrix degradation, vascularization and calcification that can be observed in the growth plate, fracture healing and OA.