Schematic showing TNF-β-induced proinflammatory and apoptotic signaling pathways in primary human chondrocytes in rheumatoid arthritis. Proinflammatory cytokines (interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α) and TNF-β) reach the synovial fluid through the bloodstream and can directly induce inflammation in chondrocytes, which leads to expression and production of cytokine receptors such as IL-1β and TNF-β receptors in the chondrocytes. TNF-β-induced inflammatory signaling in chondrocytes is further enhanced by upregulation of TNF-β production in T and B cells, by direct interaction of T and B cells with the chondrocytes and by autostimulation of the chondrocytes themselves. Downstream inflammation signaling of TNF-β in chondrocytes involves nuclear factor κB (NF-κB), leading to the production of proinflammatory mediators (IL-1β, TNF-α, TNF-β and cyclooxygenase 2 (Cox-2)), cartilage matrix degradation (matrix metalloproteinase 9 (MMP-9) and MMP-13) and apoptotic cascades (cleavage of caspase 3 and p53). The natural NF-κB inhibitor curcumin, antisense oligonucleotide against NF-κB or anti-TNF-β treatment can disrupt the TNF-β-induced inflammatory cycle through inhibition of the NF-κB signaling cascade, thus offering a promising therapeutic approach for inhibiting TNF-β-induced inflammatory environment in rheumatoid arthritis.