Fig. 1

Risk factors and pathological mechanisms of OA. Specific systemic risk factors (age, obesity, and sex) and mechanical factors (joint injury or overuse) can cause OA-like cartilage damage. Changes in the cartilage microenvironment, such as cellular secretion of matrix-degrading enzymes, reactive oxygen species, and cytokines, can accelerate the process of cartilage degeneration, resulting in the loss of the chondrocyte phenotype. The degradation products of cartilage and extracellular matrix (ECM) components can also be released into the joint cavity as damage-associated molecular patterns (DAMP) will boost the synovial cells and macrophages to secrete different types of inflammatory mediators. In addition, remodeling of the subchondral plate and calcified cartilage also reflects changes in the mechanical loading of cartilage and subchondral bone