Cellular interactions in cartilage destruction in rheumatoid arthritis. This scheme represents the progressive destruction of the cartilage associated with the invading synovial pannus in rheumatoid arthritis. As a result of immune cell interactions involving T and B lymphocytes, monocytes/macrophages, and dendritic cells, a number of different cytokines are produced in the synovium due to the influx of inflammatory cells from the circulation and synovial cell hyperplasia. The induction of proinflammatory cytokines produced primarily in the synovium, but also by chondrocytes, results in the upregulation of cartilage-degrading enzymes at the cartilage-pannus junction. Chemokines, nitric oxide (NO), and prostaglandins (PGE2) also contribute to the inflammation and tissue catabolism. ADAMTS, a disintegrin and metalloproteinase with thrombospondin-1 domains; IFN-γ, interferon-gamma; IL, interleukin; MMP, matrix metalloproteinase; SDF-1, stromal derived factor 1; TGF-β, transforming growth factor-beta; TNF-α, tumor necrosis factor-alpha; Treg, regulatory T (cell).