Figure 2.

Regulation of osteoclast differentiation by T cells in rheumatoid arthritis. Interleukin (IL)-17-producing helper T (Th17) cells have stimulatory effects on osteoclastogenesis and play an important role in the pathogenesis of rheumatoid arthritis through IL-17, whereas Th1 and Th2 cells have inhibitory effects on osteoclastogenesis through interferon-γ (IFN-γ) and IL-4, respectively. IL-17 not only induces receptor activator of nuclear factor-κB ligand (RANKL) on synovial fibroblasts of mesenchymal origin but also activates local inflammation, leading to the upregulation of proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), IL-1, and IL-6. These cytokines activate osteoclastogenesis by either acting directly on osteoclast precursor cells or inducing RANKL on synovial fibroblasts. Th17 cells also express RANKL on their cellular membrane, and this partly contributes to the enhanced osteoclastogenesis. RANK, receptor activator of nuclear factor-κB.