Osteoarthritis in the context of ageing and evolution: Loss of chondrocyte differentiation block during ageing

Ageing is the main risk factor of primary osteoarthritis (OA) and OA is the disease most strongly correlated with ageing. Both in humans and other animals OA development appears to be not strictly time-dependent but to hold pace with ageing processes. A characteristic of OA is deviant behaviour of chondrocytes in articular cartilage. These chondrocytes resemble terminal differentiated chondrocytes in growth plates and actively produce matrix degrading enzymes. The latter results in cartilage degeneration and eventually OA. We postulate that at a young age progression of chondrocyte differentiation is actively blocked in articular cartilage. This block declines when the evolutionary pressure to maintain this block, after reproductive life, is minimized. The loss of this differentiation block, maybe as a result of changes in chondrocyte TGF beta signalling, results in combination with normal joint loading in cartilage degeneration and OA.