Regulation of Osteoclast Differentiation (Identification of osteoclast and macrophage fusion protein; DC-STAMP)

Osteoclasts are bone-resorbing multinuclear cells derived from hematopoietic stem cells or monocyte/ macrophage lineage cells. Recent identification of RANK/RANKL has provided new insights into the osteoclast differentiation pathway, enabling us to generate osteoclasts without stromal cells, which support osteoclastogenesis. In order to establish a pure osteoclast culture system, we identified the osteoclast precursor cell (c-Kitc-FmsRANK cell), which is a common precursor cell of osteoclasts, macrophages and dendritic cells. Macrophages are induced by M-CSF alone, while a sequential stimulation of M-CSF followed by RANKL effectively induces osteoclast formation. Furthermore, dendritic cells are induced by GM-CSF or GM-CSF plus RANKL. Therefore, we were able to generate pure osteoclasts, macrophages or dendritic cells from the common precursor cell using specific combinations of cytokines. Using this culture system, we found that an adherent condition is critical for osteoclast differentiation. We also found that the osteoclastogenesis induced by M-CSF plus RANKL is completely inhibited by GM-CSF, and that these cells differentiate into a dendritic cell lineage. The osteoclast multinucleation is believed to be induced by cell-cell fusion of mononuclear osteoclasts. Although various molecules have been implicated in the cell-cell fusion of osteoclasts or macrophages, the essential molecule for cell fusion has not been identified. We identified that the dendritic cell-specific transmembrane protein (DC-STAMP) was an essential cell-cell fusion molecule for osteoclasts and foreign body giant cells, and that DC-STAMP deficient mice have no multinuclear osteoclasts. Here I review the osteoclast development from immature precursor cells to multinuclear osteoclasts. (J Kor Endocrinol Soc 21:347~351, 2006) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ