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

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

Research output: Contribution to journalArticle

518 Citations (Scopus)

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. JEM

Original languageEnglish
Pages (from-to)345-351
Number of pages7
JournalJournal of Experimental Medicine
Volume202
Issue number3
DOIs
Publication statusPublished - 2005 Aug 1

Fingerprint

Foreign Body Giant Cells
Cell Fusion
Osteoclasts
Dendritic Cells
Proteins
Macrophages
Osteopetrosis
Bone and Bones
Bone Remodeling
Homozygote
Giant Cells

ASJC Scopus subject areas

  • Immunology

Cite this

Yagi, M., Miyamoto, T., Sawatani, Y., Iwamoto, K., Hosogane, N., Fujita, N., ... Suda, T. (2005). DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells. Journal of Experimental Medicine, 202(3), 345-351. https://doi.org/10.1084/jem.20050645

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

In: Journal of Experimental Medicine, Vol. 202, No. 3, 01.08.2005, p. 345-351.

Research output: Contribution to journalArticle

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 2005, 'DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells', Journal of Experimental Medicine, vol. 202, no. 3, pp. 345-351. https://doi.org/10.1084/jem.20050645
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. / DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells. In: Journal of Experimental Medicine. 2005 ; Vol. 202, No. 3. pp. 345-351.
@article{91ffbb4a218a46baa962e447ffe3e677,
title = "DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells",
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. JEM",
author = "Mitsuru Yagi and Takeshi Miyamoto and Yumi Sawatani and Katsuya Iwamoto and Naobumi Hosogane and Nobuyuki Fujita and Kozo Morita and Ken Ninomiya and Toru Suzuki and Kana Miyamoto and Yuichi Oike and Motohiro Takeya and Yoshiaki Toyama and Toshio Suda",
year = "2005",
month = "8",
day = "1",
doi = "10.1084/jem.20050645",
language = "English",
volume = "202",
pages = "345--351",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "3",

}

TY - JOUR

T1 - DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells

AU - Yagi, Mitsuru

AU - Miyamoto, Takeshi

AU - Sawatani, Yumi

AU - Iwamoto, Katsuya

AU - Hosogane, Naobumi

AU - Fujita, Nobuyuki

AU - Morita, Kozo

AU - Ninomiya, Ken

AU - Suzuki, Toru

AU - Miyamoto, Kana

AU - Oike, Yuichi

AU - Takeya, Motohiro

AU - Toyama, Yoshiaki

AU - Suda, Toshio

PY - 2005/8/1

Y1 - 2005/8/1

N2 - 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. JEM

AB - 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. JEM

UR - http://www.scopus.com/inward/record.url?scp=23744459835&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23744459835&partnerID=8YFLogxK

U2 - 10.1084/jem.20050645

DO - 10.1084/jem.20050645

M3 - Article

C2 - 16061724

AN - SCOPUS:23744459835

VL - 202

SP - 345

EP - 351

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 3

ER -