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

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

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Yagi, Mitsuru, Miyamoto, Takeshi, Sawatani, Yumi, Iwamoto, Katsuya, Hosogane, Naobumi, Fujita, Nobuyuki, Morita, Kozo, Ninomiya, Ken, Suzuki, Toru, Miyamoto, Kana, Oike, Yuichi, Takeya, Motohiro, Toyama, Yoshiaki, Suda, Toshio·2005·The Journal of Experimental Medicine

DOI 10.1084/jem.20050645PMC PMC2213087

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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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BindingDB Entry 50046372: Novel inhibitors of RANKL-induced osteoclastogenesis: Design, synthesis, and biological evaluation of 6-(2,4-difluorophenyl)-3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-diones.
BindingDB (2016) · UC San Diego · doi:10.7270/q2v126kk
Intercellular communication networks in the osteoporotic bone microenvironment
Li, Y., Liu, X., Feng, X., Li, X., & Yin, H. (2026) · Connective Tissue Research · doi:10.1080/03008207.2026.2752398

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
ORCID: Yagi, Mitsuru
Miyamoto, Takeshi
Fujita, Nobuyuki
Miyamoto, Kana
Oike, Yuichi
Takeya, Motohiro
Suda, Toshio
Venue: The Journal of Experimental Medicine
Publisher: Rockefeller University Press
Published: 2005-08-01
Volume: 202
Issue: 3
Pages: 345-351
ISSN: 0022-1007 (ISSN-L)
1540-9538
DOI: 10.1084/jem.20050645
PMC: PMC2213087
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: bronze
doi.org
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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DC-STAMP is essential for cell–cell fusion in osteoclasts and foreign body giant cells

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