The Journal of Experimental Medicine
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Published online 27 September 2004 doi:10.1084/jem.20040518
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 7, 941-946
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Brief Definitive Report

 RANKL-induced DC-STAMP Is Essential for Osteoclastogenesis

Toshio Kukita1, Naohisa Wada1, Akiko Kukita2, Takashi Kakimoto2, Ferry Sandra1, Kazuko Toh1, Kengo Nagata1, Tadahiko Iijima1, Madoka Horiuchi3,4, Hiromi Matsusaki4, Kunio Hieshima5, Osamu Yoshie5, and Hisayuki Nomiyama3

1 Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan
2 Department of Microbiology, Saga Medical School, Saga 849-8501, Japan
3 Department of Molecular Enzymology, Kumamoto University Graduate School of Medical Sciences, Kumamoto 860-8556, Japan
4 Faculty of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto 862-8502, Japan
5 Department of Microbiology, Solution Oriented Research for Science and Technology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan

Address correspondence to Hisayuki Nomiyama, Dept. of Molecular Enzymology, Kumamoto University Graduate School of Medical Sciences, Kumamoto 860-8556, Japan. Phone: 81-96-373-5065; Fax: 81-96-373-5066; email: nomiyama{at}gpo.kumamoto-u.ac.jp

Osteoclasts are bone-resorbing, multinucleated giant cells that are essential for bone remodeling and are formed through cell fusion of mononuclear precursor cells. Although receptor activator of nuclear factor–{kappa}B ligand (RANKL) has been demonstrated to be an important osteoclastogenic cytokine, the cell surface molecules involved in osteoclastogenesis are mostly unknown. Here, we report that the seven-transmembrane receptor-like molecule, dendritic cell–specific transmembrane protein (DC-STAMP) is involved in osteoclastogenesis. Expression of DC-STAMP is rapidly induced in osteoclast precursor cells by RANKL and other osteoclastogenic stimulations. Targeted inhibition of DC-STAMP by small interfering RNAs and specific antibody markedly suppressed the formation of multinucleated osteoclast-like cells. Overexpression of DC-STAMP enhanced osteoclastogenesis in the presence of RANKL. Furthermore, DC-STAMP directly induced the expression of the osteoclast marker tartrate-resistant acid phosphatase. These data demonstrate for the first time that DC-STAMP has an essential role in osteoclastogenesis.

Key Words: osteoclast • cell fusion • adhesion • seven-transmembrane receptor • TRAP


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