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.
Skip Nav Destination
Article navigation
1 August 2005
Brief Definitive Report|
August 01 2005
DC-STAMP is essential for cell–cell fusion in osteoclasts and foreign body giant cells
Mitsuru Yagi,
Mitsuru Yagi
1Department of Cell Differentiation, The Sakaguchi Laboratory
2Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Search for other works by this author on:
Takeshi Miyamoto,
Takeshi Miyamoto
1Department of Cell Differentiation, The Sakaguchi Laboratory
2Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Search for other works by this author on:
Yumi Sawatani,
Yumi Sawatani
1Department of Cell Differentiation, The Sakaguchi Laboratory
3Department of Oral Surgery, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 862-0811, Japan
Search for other works by this author on:
Katsuya Iwamoto,
Katsuya Iwamoto
1Department of Cell Differentiation, The Sakaguchi Laboratory
4Department of Orthopedic Surgery, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 862-0811, Japan
Search for other works by this author on:
Naobumi Hosogane,
Naobumi Hosogane
1Department of Cell Differentiation, The Sakaguchi Laboratory
2Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Search for other works by this author on:
Nobuyuki Fujita,
Nobuyuki Fujita
1Department of Cell Differentiation, The Sakaguchi Laboratory
2Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Search for other works by this author on:
Kozo Morita,
Kozo Morita
1Department of Cell Differentiation, The Sakaguchi Laboratory
2Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Search for other works by this author on:
Ken Ninomiya,
Ken Ninomiya
1Department of Cell Differentiation, The Sakaguchi Laboratory
2Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Search for other works by this author on:
Toru Suzuki,
Toru Suzuki
1Department of Cell Differentiation, The Sakaguchi Laboratory
2Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Search for other works by this author on:
Kana Miyamoto,
Kana Miyamoto
1Department of Cell Differentiation, The Sakaguchi Laboratory
6First Department of Internal Medicine, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan
Search for other works by this author on:
Yuichi Oike,
Yuichi Oike
1Department of Cell Differentiation, The Sakaguchi Laboratory
Search for other works by this author on:
Motohiro Takeya,
Motohiro Takeya
5Second Department of Pathology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 862-0811, Japan
Search for other works by this author on:
Yoshiaki Toyama,
Yoshiaki Toyama
2Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Search for other works by this author on:
Toshio Suda
Toshio Suda
1Department of Cell Differentiation, The Sakaguchi Laboratory
Search for other works by this author on:
Mitsuru Yagi
1Department of Cell Differentiation, The Sakaguchi Laboratory
2Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Takeshi Miyamoto
1Department of Cell Differentiation, The Sakaguchi Laboratory
2Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Yumi Sawatani
1Department of Cell Differentiation, The Sakaguchi Laboratory
3Department of Oral Surgery, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 862-0811, Japan
Katsuya Iwamoto
1Department of Cell Differentiation, The Sakaguchi Laboratory
4Department of Orthopedic Surgery, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 862-0811, Japan
Naobumi Hosogane
1Department of Cell Differentiation, The Sakaguchi Laboratory
2Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Nobuyuki Fujita
1Department of Cell Differentiation, The Sakaguchi Laboratory
2Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Kozo Morita
1Department of Cell Differentiation, The Sakaguchi Laboratory
2Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Ken Ninomiya
1Department of Cell Differentiation, The Sakaguchi Laboratory
2Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Toru Suzuki
1Department of Cell Differentiation, The Sakaguchi Laboratory
2Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Kana Miyamoto
1Department of Cell Differentiation, The Sakaguchi Laboratory
6First Department of Internal Medicine, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan
Yuichi Oike
1Department of Cell Differentiation, The Sakaguchi Laboratory
Motohiro Takeya
5Second Department of Pathology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 862-0811, Japan
Yoshiaki Toyama
2Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Toshio Suda
1Department of Cell Differentiation, The Sakaguchi Laboratory
CORRESPONDENCE Takeshi Miyamoto: [email protected] OR Toshio Suda: [email protected]
M. Yagi and T. Miyamoto contributed equally to this work.
Received:
March 30 2005
Accepted:
June 07 2005
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2005
J Exp Med (2005) 202 (3): 345–351.
Article history
Received:
March 30 2005
Accepted:
June 07 2005
Citation
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; DC-STAMP is essential for cell–cell fusion in osteoclasts and foreign body giant cells . J Exp Med 1 August 2005; 202 (3): 345–351. doi: https://doi.org/10.1084/jem.20050645
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionEmail alerts
Advertisement