RANKL-induced DC-STAMP Is Essential for Osteoclastogenesis

  • Toshio Kukita
    1Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan
  • Naohisa Wada
    1Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan
  • Akiko Kukita
    2Department of Microbiology, Saga Medical School, Saga 849-8501, Japan
  • Takashi Kakimoto
    2Department of Microbiology, Saga Medical School, Saga 849-8501, Japan
  • Ferry Sandra
    1Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan
  • Kazuko Toh
    1Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan
  • Kengo Nagata
    1Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan
  • Tadahiko Iijima
    1Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan
  • Madoka Horiuchi
    3Department of Molecular Enzymology, Kumamoto University Graduate School of Medical Sciences, Kumamoto 860-8556, Japan
  • Hiromi Matsusaki
    4Faculty of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto 862-8502, Japan
  • Kunio Hieshima
    5Department of Microbiology, Solution Oriented Research for Science and Technology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan
  • Osamu Yoshie
    5Department of Microbiology, Solution Oriented Research for Science and Technology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan
  • Hisayuki Nomiyama
    3Department of Molecular Enzymology, Kumamoto University Graduate School of Medical Sciences, Kumamoto 860-8556, Japan

抄録

<jats:p>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–κB 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.</jats:p>

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