J Korean Endocr Soc.  2006 Oct;21(5):347-351. 10.3803/jkes.2006.21.5.347.

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

• Miyamoto T

• KMID: 1511982
• DOI: http://doi.org/10.3803/jkes.2006.21.5.347

Abstract

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-Kit(+)c-Fms(+)RANK(-) 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.

Keyword

Cell-cell fusion; DC-STAMP; Foreign body giant cells; Osteoclasts

MeSH Terms

Animals
Cell Fusion
Cytokines
Dendritic Cells
Giant Cells, Foreign-Body
Granulocyte-Macrophage Colony-Stimulating Factor
Hematopoietic Stem Cells
Macrophage Colony-Stimulating Factor
Macrophages*
Mice
Osteoclasts*
Stromal Cells
Cytokines
Granulocyte-Macrophage Colony-Stimulating Factor
Macrophage Colony-Stimulating Factor

Figure

• 

  Fig. 1 Osteoclast, macrophage and dendritic cell differentiation from common precursor cells. Macrophages are induced by M-CSF alone, while osteoclasts are induced by M-CSF followed by RANKL stimulation. Immature dendritic cells are induced by GM-CSF alone, and GM-CSF plus RANKL induces activated dendritic cells. The osteoclastogenesis induced by M-CSF and RANKL is completely inhibited by GM-CSF, and that cells differentiate into dendritic cell lineage cells.

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