Osteoblasts induce Ca2+ oscillation-independent NFATc1 activation during osteoclastogenesis.
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 Ca(2+) oscillation-independent osteoclastogenesis. We found that bone marrow-derived monocyte/macrophage precursor cells (BMMs) lacking inositol 1,4,5-trisphosphate receptor type2 (IP(3)R2) did not exhibit Ca(2+) oscillation or differentiation into multinuclear osteoclasts in response to recombinant receptor activator of NF-kappaB ligand/macrophage colony-stimulating factor stimulation. IP(3)R2 knockout BMMs, however, underwent osteoclastogenesis when they were cocultured with osteoblasts or in vivo in the absence of Ca(2+) 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 NFATc1 activation, leading to efficient osteoclastogenesis in vivo.
Division of Molecular Neurobiology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan.
Yukiko
Y
Kuroda
Chihiro
C
Hisatsune
Takeshi
T
Nakamura
Koichi
K
Matsuo
Katsuhiko
K
Mikoshiba
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002450:Cell Communication; D002454:Cell Differentiation; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism; D015398:Signal Transduction
D053496:Inositol 1,4,5-Trisphosphate Receptors; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D053245:RANK Ligand; D002118:Calcium