Mechanoadaptation: articular cartilage through thick and thin

The articular cartilage is exquisitely sensitive to mechanical load. Its structure is largely defined by the mechanical environment and destruction in osteoarthritis is the pathophysiological consequence of abnormal mechanics. It is often overlooked that disuse of joints causes profound loss of volume in the articular cartilage, a clinical observation first described in polio patients and stroke victims. Through the 1980s, the results of studies exploiting experimental joint immobilisation supported this. Importantly, this substantial body of work was also the first to describe metabolic changes that resulted in decreased synthesis of matrix molecules, especially sulfated proteoglycans. The molecular mechanisms that underlie disuse atrophy are poorly understood despite the identification of multiple mechanosensing mechanisms in cartilage. Moreover, there has been a tendency to equate cartilage loss with osteoarthritic degeneration. Here, we review the historic literature and clarify the structural, metabolic and clinical features that clearly distinguish cartilage loss due to disuse atrophy and those due to osteoarthritis. We speculate on the molecular sensing pathways in cartilage that may be responsible for cartilage mechanoadaptation. Cartilage atrophy is distinct to osteoarthritic damage. In normal full‐thickness cartilage (left panel) chondrocytes are diffusely distributed through a proteoglycan‐rich (light pink) articular cartilage matrix separated from calcified cartilage beneath by a tidemark. Cartilage atrophy (middle panel) is associated with thinning of the cartilage and reduced proteoglycan content but the articular surface is intact. In contrast, osteoarthritic tissue (right hand panel), whilst also associated with thinning, has marked surface damage and patchy proteoglycan staining.