Figure 3

Effects of inflammation on bone. Processes stimulating bone growth (green arrows) and processes leading to bone loss (red arrows). The proinflammatory cytokine tumor necrosis factor alpha (TNFα) induces expression of Dickkopf-1 (Dkk-1) in synovial fibroblasts, which inhibits the Wnt signaling pathway. This results in decreased osteoblastogenesis and bone formation. Simultaneously, osteoclastic bone resorption is stimulated via receptor activator of nuclear factor-κB ligand (RANKL). Proinflammatory mediators stimulate osteoblasts to release macrophage colony-stimulating factor (M-CSF), stimulating osteoclastogenesis. Osteoprotegerin (OPG) is also released by osteoblasts and binds RANKL, thereby inhibiting osteoclastogenesis. RANK, receptor activator of nuclear factor-κB. Figure reproduced with permission from [130].