Figure 2

Cartoon of healthy and OA knee joints. Shown is a healthy joint, in which physiological loading (magnitude of load×frequency of loading) is managed by the joint. Healthy subchondral blood vessels and blood perfusion, and a putative healthy crosstalk between the subchondral bone and articular cartilage lead to coupled bone remodeling to maintain homeostasis and repair microdamage in the bone matrix. In the OA joint, chronic overloading results in failed repair mechanisms. Bone within a bone marrow lesion (BML) zone, imaged by MRI, contains the most severe bony manifestations, in which dysregulated bone remodeling results in both bone attrition and sclerosis. The cartilage overlying the BML is degraded, with increased matrix proteases and decreased production of cartilage matrix. A putative unhealthy crosstalk between the bone and cartilage compartments exacerbates the failure of repair mechanisms, in the face of continued unfavourable biomechanics.