Figure 2: Schematic of the interplay between the extracellular matrix and cellular activities under inflammation during the progression of osteoarthritis (OA). Wear and tear or trauma induces inflammation and mechanical defects in cartilage, which initiate OA. These altered microenvironments affect the residential chondrocytes to produce nonchondrocytic extracellular matrix (ECM) that, in turn, further drives the dedifferentiation of the chondrocytes. The changes in microenvironments also negatively affect the chondrogenic differentiation of mesenchymal stem cells that originate from subchondral bone marrow, preventing the self-regeneration of cartilage. The positive feedback loop between mal-formed ECM and cellular activities drives the progression of OA.