RANKL-induced DC-STAMP is essential for osteoclastogenesis

Toshio Kukita, Naohisa Wada, Akiko Kukita, Takashi Kakimoto, Ferry Sandra, Kazuko Toh, Kengo Nagata, Tadahiko Iijima, Madoka Horiuchi, Hiromi Matsusaki, Kunio Hieshima, Osamu Yoshie, Hisayuki Nomiyama

Research output: Contribution to journalArticlepeer-review

199 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)941-946
Number of pages6
JournalJournal of Experimental Medicine
Issue number7
Publication statusPublished - Oct 4 2004

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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