Cited by 892Bone Metabolism and DiseasesPhagocytosis and Immune RegulationOsteomyelitis and Bone Disorders Research

The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.

DC-STAMP is essential for cell–cell fusion in osteoclasts and foreign body giant cells

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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.

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  1. 1995, Am. J. Pathol., 147, 1487

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Metadata

Authors
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., & Suda, T.
Affiliations
  • Keio University (JP)
  • Kumamoto University (JP)
  • Kyushu University (JP)
  • 1Department of Cell Differentiation, The Sakaguchi Laboratory
Venue
The Journal of Experimental Medicine
Published
2005-08-01
Volume
202
Issue
3
Pages
345-351
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
OpenAlex
W2111239144
Cited by
890
References
24
Citations by year
2026: 36 · 2025: 35 · 2024: 33 · 2023: 36 · 2022: 56 · 2021: 48 · 2020: 60 · 2019: 39 · 2018: 40 · 2017: 52 · 2016: 48 · 2015: 48 · 2014: 50 · 2013: 37 · 2012: 46
FWCI
11.80
Type
journal article
Language
en
Open access
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
Keywords
DC-STAMP, cell fusion, osteoclasts, foreign body giant cells, multinucleation, osteoclastogenesis, bone resorption, osteopetrosis, macrophages, bone homeostasis, seven-transmembrane proteins
MeSH terms
Animals, Bone and Bones, Bone Resorption, Cell Fusion, Homeostasis, Macrophages, Membrane Proteins, Nerve Tissue Proteins, Osteoclasts, Giant Cells, Mice, Knockout, Mice

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