Figure 1.

The pathology and pathophysiology of Knee osteoarthritis (KOA). Normal wear and tear, abnormal mechanical loading, injury, and aging are common causes to damage articular cartilage, as well as subchondral bone, synovial tissue and ligaments, which could change the molecular composition and organization in the extracellular matrix. Under the stimulation, injured chondrocytes produce the matrix metalloproteinases (MMP-1, MMP-3, and MMP-13) and the ADAMTSs (ADAMTS-4 and ADAMTS-5). They thus contribute to declining levels of proteoglycans, aggrecan, and type II collagen in the cartilage matrix by inhibiting the synthesis of key components of the extracellular matrix, which eventually leads to cartilage degeneration.