New roles of osteoblasts involved in osteoclast differentiation

Figure 1 Regulation of osteoclast differentiation by osteoblasts through macrophage colony-stimulating factor, receptor activator of nuclear factor-κB ligand, and osteoprotegerin production. Osteoblasts express two cytokines essential for osteoclast differentiation, macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). Osteoblasts constitutively express M-CSF. On the other hand, osteoblasts express RANKL as a membrane-associated form in response to bone resorption-stimulating factors such as 1α,25-dihydroxyvitamin D3 [1α,25(OH)₂D₃], parathyroid hormone (PTH), prostaglandin E₂ (PGE₂), and interleukin 11 (IL-11). Osteoclast precursors express c-Fms (M-CSF receptor) and RANK (RANKL receptor) and differentiate into osteoclasts in the presence of M-CSF and RANKL. Osteoblasts also produce osteoprotegerin (OPG), which inhibits osteoclastogenesis by blocking the RANKL-RANK interaction.