Fig. 1

The inflammatory network and pathobiology in OA. a Risk factors for OA. Evidence suggests that specific systemic risk factors (e.g., age, obesity, and sex) and mechanical factors (e.g., trauma and joint biomechanics) are capable of causing cartilage damage in OA. b Inflammatory network in OA. The degradation products of cartilage and extracellular matrix (ECM) components are released into the joint cavity as damage-associated molecular patterns (DAMPs), which ultimately stimulate synovial cells and macrophages to secrete different types of inflammatory mediators, such as cytokines, chemokines, and complement. These molecules further lead to loss of chondrocyte phenotype and cartilage damage. Notably, the fat pad around the joints has been identified as another source of proinflammatory cytokines, especially adipokines, which may also trigger a catabolic response in chondrocytes. c Changes of osteochondral structure in OA. With the progression of OA, hypertrophy, senscent, and apoptotic chondrocytes increase, resulting in ECM catabolism as well as cracks and stratification appearing on the surface of cartilage. In the subchondral bone region, subchondral bone thickness gradually increases and calcified cartilage extends into articular cartilage, with duplication of the tidemark and invasion of vascular and nerve invasion into the cartilage region. Overall, these changes in the cartilage microenvironment can accelerate the degeneration progression of cartilage. MMPs matrix metalloproteinases, ADAMTSs a disintegrin and metalloproteinase with thrombospondin motifs, ECM extracellular matrix, DAMPs damage-associated molecular patterns, IL-1β interleukin-1beta, IL-6 interleukin-6, TNF-α tumor necrosis factor-alpha, CCL2 chemokine (C-C motif) ligand 2, CCL5 chemokine (C-C motif) ligand 5, TGF-β transforming growth factor-beta, TLR2 Toll-like receptor 2, TLR4 Toll-like receptor 4