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PMID:16061724

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Citation

Yagi, M, Miyamoto, T, Sawatani, Y, Iwamoto, K, Hosogane, N, Fujita, N, Morita, K, Ninomiya, K, Suzuki, T, Miyamoto, K, Oike, Y, Takeya, M, Toyama, Y and Suda, T (2005) DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells. J. Exp. Med. 202:345-51

Abstract

Osteoclasts are bone-resorbing cells that play a pivotal role in bone remodeling. Osteoclasts form large multinuclear giant cells by fusion of mononuclear osteoclasts. How cell fusion is mediated, however, is unclear. We identify the dendritic cell-specific transmembrane protein (DC-STAMP), a putative seven-transmembrane protein, by a DNA subtraction screen between multinuclear osteoclasts and mononuclear macrophages. DC-STAMP is highly expressed in osteoclasts but not in macrophages. DC-STAMP-deficient mice were generated, and osteoclast cell fusion was completely abrogated in homozygotes despite normal expression of osteoclast markers and cytoskeletal structure. As osteoclast multinucleation was restored by retroviral introduction of DC-STAMP, loss of cell fusion was directly attributable to a lack of DC-STAMP. Defects in osteoclast multinucleation reduce bone-resorbing activity, leading to osteopetrosis. Similar to osteoclasts, foreign body giant cell formation by macrophage cell fusion was also completely abrogated in DC-STAMP-deficient mice. We have thus identified an essential regulator of osteoclast and macrophage cell fusion, DC-STAMP, and an essential role of osteoclast multinucleation in bone homeostasis.

Links

PubMed PMC2213087 Online version:10.1084/jem.20050645

Keywords

Animals; Bone Resorption/genetics; Bone Resorption/metabolism; Bone and Bones/cytology; Bone and Bones/physiology; Cell Fusion; Giant Cells/cytology; Giant Cells/physiology; Homeostasis/genetics; Homeostasis/physiology; Macrophages/cytology; Macrophages/physiology; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mice; Mice, Knockout; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Osteoclasts/cytology; Osteoclasts/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:DCSTP

involved_in

GO:0034241: positive regulation of macrophage fusion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DCSTP

involved_in

GO:0061025: membrane fusion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DCSTP

involved_in

GO:0045780: positive regulation of bone resorption

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DCSTP

involved_in

GO:0072675: osteoclast fusion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DCSTP

involved_in

GO:0071356: cellular response to tumor necrosis factor

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DCSTP

involved_in

GO:0036006: cellular response to macrophage colony-stimulating factor stimulus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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