DC-STAMP is essential for cell–cell fusion in osteoclasts and foreign body giant cells
Open accessAbstract
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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Macrophage fusion was completely abrogated in DC-STAMP deficient mice.
“Macrophage fusion was completely abrogated in DC-STAMP deficient mice.[68]”
From Foreign body reaction to biomaterials (2008) · cites this paper as [68]
DC-STAMP is necessary for fusion in the formation of FBGCs.
“Dendritic cell-specific transmembrane protein (DC-STAMP) is necessary for fusion in the formation of FBGCs.”
From Foreign body reaction to biomaterials (2008) · cites this paper as [68]
NBPs induce osteoclasts to acquire a nonresorbing phenotype by inhibiting c-Src and stimulating DC-STAMP.
“NPBs induce osteoclasts to acquire a nonresorbing phenotype by inhibiting c-Src, which is essential for cytoskeletal construction,158 and by stimulating dendritic cell-specific transmembrane protein (DC-STAMP),159 which is necessary for cell fusion.”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [159]
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- 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
- 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
- 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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