Osteoblasts induce Ca2+ oscillation-independent NFATc1 activation during osteoclastogenesis

Yukiko Kuroda, Chihiro Hisatsune, Takeshi Nakamura, Koichi Matsuo, Katsuhiko Mikoshiba

Research output: Contribution to journalArticlepeer-review

116 Citations (Scopus)


Intercellular cross-talk between osteoblasts and osteoclasts is important for controlling bone remolding and maintenance. However, the precise molecular mechanism by which osteoblasts regulate osteoclastogenesis is still largely unknown. Here, we show that osteoblasts can induce Ca2+ oscillation-independent osteoclastogenesis. We found that bone marrow-derived monocyte/macrophage precursor cells (BMMs) lacking inositol 1,4,5-trisphosphate receptor type2 (IP3R2)did not exhibit Ca2+ oscillation or differentiation into multinuclear osteoclasts in response to recombinant receptor activator of NF-κB Ligand/macrophage colony-stimulating factor stimulation. IP3R2 knockout BMMs, however, underwent osteoclastogenesis when they were cocultured with osteoblasts or in vivo in the absence of Ca2+ oscillation. Furthermore, we found that Ca 2+ oscillation-independent osteoclastogenesis was insensitive to FK506, a calcineurin inhibitor. Taken together, we conclude that both Ca 2+ oscillation/calcineurin-dependent and -independent signaling pathways contribute to NFAT1 activation, leading to efficient osteoclastogenesis in vivo.

Original languageEnglish
Pages (from-to)8643-8648
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number25
Publication statusPublished - 2008 Jun 24


  • Calcium
  • Differentiation
  • Inositol 1,4,5-trisphosphate receptor (IP3R)
  • Osteoclast
  • Receptor activator of NF-κB ligand (RANKL)

ASJC Scopus subject areas

  • General


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