The pathology of rheumatoid arthritis (RA) and the mechanism of cartilage and bone destruction. RA is characterized by proliferative synovium (pannus) and an excessive immune response of T-cells. Pannus comprises T-cells, synovial fibroblasts, and macrophages that produce inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin-1 (IL-1), IL-6, and IL-17. These inflammatory cytokines activate osteoclasts, leading to bone destruction. T-helper (Th) cells have subsets such as Th1, Th2, and Th17 cells. Naive T-cells differentiate into Th17 cells through IL-1β, IL-6, IL-21, and transforming growth factor-β (TGF-β). Th17 cells produce IL-17 that activates inflammation by acting on various immune cells and activates osteoclasts by inducing the receptor activator of nuclear factor kappa B ligand (RANKL) in synovial fibroblasts. IFN-γ, IL-4, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), produced by Th1, Th2, and Treg, respectively, regulate osteoclast differentiation. Cartilage destruction is caused by matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) produced by chondrocytes, synovial fibroblasts, and synovial macrophages.