Dimer formation of receptor activator of nuclear factor κB induces incomplete osteoclast formation

Katsuya Iwamoto, Takeshi Miyamoto, Yumi Sawatani, Naobumi Hosogane, Isao Hamaguchi, Masamichi Takami, Kana Nomiyama, Katsumasa Takagi, Toshio Suda

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Receptor activator of nuclear factor κB-ligand (RANKL) transduces a differentiation signal appropriate to osteoclasts likely through induction a receptor homotrimer; however, biological importance of RANK-trimerizarion is unknown. To address the signaling mechanism of the RANK receptor, we analyzed the effect of two different types of homodimer inducers RANK-TM-FKBP36v and hEpoR-RANK-TM on osteoclastogenesis. Dimerizing component FKBP36v or extracellular portion of human erythropoietin receptor (hEpoR) was fused to RANK lacking the extracellular domain, and the dimerization of this fusion protein was induced by addition of the chemical inducer of dimerization AP20187 or erythropoietin, respectively. Such treatment resulted in induction of TRAP-activity, a marker of osteoclast in a dose dependent manner, with an efficiency equivalent to that of induction by RANKL. However, dimerized-RANK-induced osteoclasts showed relatively low levels of multinucleation, pit forming activity, and expression of calcitonin receptor and cathepsin K, compared with osteoclasts which were induced in the presence of RANKL. As expression of nuclear factor of activated T cells 1 (NFATc1) was also reduced in dimerized-RANK-induced osteoclasts, RANK oligomerization by RANKL is a critical event to generate fully matured osteoclasts through upregulation of NFATc1.

Original languageEnglish
Pages (from-to)229-234
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume325
Issue number1
DOIs
Publication statusPublished - 2004 Dec 3

Keywords

  • Differentiation
  • FKBP36v
  • NFATc1
  • Osteoclast
  • RANK

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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