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PMID:17164993

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Citation

Miyamoto, T (2006) The dendritic cell-specific transmembrane protein DC-STAMP is essential for osteoclast fusion and osteoclast bone-resorbing activity. Mod Rheumatol 16:341-2

Abstract

Osteoclasts are bone-resorbing cells that play a critical role for bone destruction in rheumatoid arthritis. It is well known that osteoclasts form multinuclear cells by cell-cell fusion of mononuclear osteoclasts; however, what molecules are required for osteoclast cell-cell fusion, and the role of multinucleation remain uncharacterized. We identified the dendritic cell-specific transmembrane protein DC-STAMP, a putative seven transmembrane protein, and generated DC-STAMP-deficient mice. The cell fusion of osteoclasts was completely abrogated in DC-STAMP-deficient mice, while the transcription factors required for osteoclast differentiation or osteoclast maturation markers were induced as wild type osteoclasts. Interestingly, bone-resorbing activity was reduced in DC-STAMP-deficient osteoclasts compared with wild-type osteoclasts, and DC-STAMP-deficient mice showed osteopetrosis. Thus, we identified DC-STAMP as an essential molecule for osteoclast cell-cell fusion, and found that multinuclear osteoclasts have a higher bone-resorbing activity than mononuclear osteoclastic cells seen in DC-STAMP-deficient mice.

Links

PubMed Online version:10.1007/s10165-006-0524-0

Keywords

Animals; Arthritis, Rheumatoid/metabolism; Arthritis, Rheumatoid/pathology; Bone Resorption/metabolism; Bone Resorption/pathology; Cell Fusion; Dendritic Cells/metabolism; Giant Cells/metabolism; Giant Cells/pathology; Giant Cells/physiology; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mice; Mice, Knockout; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Osteoclasts/metabolism; Osteoclasts/pathology; Osteoclasts/physiology; Osteopetrosis/genetics; Osteopetrosis/metabolism; Osteopetrosis/pathology

Significance

Annotations

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

MOUSE:DCSTP

involved_in

GO:0061025: membrane fusion

ECO:0000315: mutant phenotype 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:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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