Mechanoadaptation: articular cartilage through thick and thin

Abstract

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.

Keywords: articular cartilage; cartilage hypertrophy; disuse atrophy; mechanoadaptation; mechanotransduction; osteoarthritis.

Figure 1. Schematic diagram of articular cartilage

Illustration of tertiary structure of fibrillar collagens in articular cartilage showing parallel arrangement in superficial layer and perpendicular orientation in deeper layers. Arrows show direction of mechanical load and how it is dissipated across the articulating surface.

Figure 2. Schematic diagram of a chondron

Illustration of the chondrocyte sitting within its pericellular matrix (PCM), together forming the chondron. Note absence of fibrillar collagens and aggrecan in the PCM, but abundance in the adjacent territorial matrix. Multiple heparan sulfate‐bound growth factors are bound within the PCM and released upon tissue compression or injury.