RANKL-induced DC-STAMP is essential for osteoclastogenesis

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-kappaB ligand (RANKL) has been demonstrated to be an important osteoclastogenic cytokine,...

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Bibliographic Details
Published in:The Journal of experimental medicine 2004-10, Vol.200 (7), p.941-946
Main Authors: Kukita, Toshio, Wada, Naohisa, Kukita, Akiko, Kakimoto, Takashi, Sandra, Ferry, Toh, Kazuko, Nagata, Kengo, Iijima, Tadahiko, Horiuchi, Madoka, Matsusaki, Hiromi, Hieshima, Kunio, Yoshie, Osamu, Nomiyama, Hisayuki
Format: Article
Language:English
Subjects:
Acid Phosphatase - genetics
Acid Phosphatase - metabolism
Animals
Blotting, Northern
Brief Definitive Report
Carrier Proteins - metabolism
Carrier Proteins - physiology
Cells, Cultured
Dendritic Cells - metabolism
Gene Expression Regulation
Immunohistochemistry
Isoenzymes - genetics
Isoenzymes - metabolism
Membrane Glycoproteins - metabolism
Membrane Glycoproteins - physiology
Membrane Proteins - metabolism
Membrane Proteins - physiology
Mice
Oligonucleotides
Osteoclasts - physiology
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
RNA, Small Interfering - genetics
Tartrate-Resistant Acid Phosphatase
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Summary: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-kappaB 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.
ISSN:0022-1007
1540-9538
1892-1007
DOI:10.1084/jem.20040518