Figure 1

Pathways for osteogenesis and osteoclastogenesis. Osteoblasts mature from mesenchymal stem cells to preosteoblasts. The Wnt signaling pathway antagonists (DKK-1, sclerostin, and SFRP1) and serotonin all inhibit osteogenesis. A number of cell types can synthesize Wnt signaling antagonists. Fibroblast-like synoviocytes from rheumatoid arthritis patients after stimulation with TNF-α, and myeloma cells synthesize DKK-1 and osteocytes synthesize sclerostin. Osteoblasts also now are known to be the main controllers of osteoclastogenesis through the production of RANKL by pre-osteoblast cells. The antagonist of RANKL, OPG, is produced by mature osteoblasts and prevents RANKL from binding to its receptor, RANK, so that osteoclast maturation and activity are inhibited. DKK, dickkopf; OPG, osteoprotegerin; RANKL, receptor activator of nuclear factor-κB ligand; SFRP, secreted frizzled-related protein; TNF, tumor necrosis factor.