Fig. 1

Overview of the healthy and osteoarthritic joint along with the pathophysiology of OA. A Healthy joint is depicted: intact cartilage with no fissures and synovial inflammation signs. Osteoarthritis is characterized by soft tissue swelling, osteophyte formation, meniscus deterioration, and degeneration of cartilage. B Cartilage breakdown products are released from the damaged cartilage tissue into the joint space, which are phagocytosed by the synovial cells and infiltrated macrophages, intensifying synovial inflammation. In the inflamed synovium, pro-inflammatory and catabolic mediators are produced by the activated synovial cells that cause overproduction of the proteolytic enzymes, establishing a positive feedback loop. The activated synovial B cells, T cells, and infiltrating macrophages amplify the inflammatory response. To neutralize this inflammatory response, anti-inflammatory cytokines are produced by the synoviocytes and chondrocytes. Furthermore, the inflamed macrophages contribute to the synovial angiogenesis and osteophyte formation via VEGF and BMPs release, respectively. Panel B is adapted from Sellam et al. [27] with permission, copyright 2010, Springer Nature. (The figure was prepared with Biorender). ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs; BMP, bone morphogenetic protein; IL, interleukin; IL-1Ra, IL-1 receptor antagonist; LTB4, leukotriene B4; MMP, matrix metalloproteinase; NO, nitric oxide; OA, osteoarthritis; PGE2, prostaglandin E2; TIMP, tissue inhibitor of metalloproteinase; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor