Osteoblasts induce Ca2+ oscillation-independent NFATc1 activation during osteoclastogenesis
Osteoblasts induce Ca2+ oscillation-independent NFATc1 activation during osteoclastogenesis
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DOI：
10.1073/pnas.0800642105
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发表时间：
2008-06-24
影响因子：
11.1
通讯作者：
Mikoshiba, Katsuhiko
中科院分区：
文献类型：
--
作者：
Kuroda, Yukiko;Hisatsune, Chihiro;Mikoshiba, Katsuhiko
成骨细胞和破骨细胞之间的细胞间串扰对于控制骨重塑和维持是重要的。然而，成骨细胞调节破骨细胞生成的确切分子机制仍不清楚。在这里，我们表明，成骨细胞可以诱导钙振荡独立的破骨细胞。我们发现缺乏1，4，5-三磷酸肌醇受体2型（IP（3）R2）的骨髓来源的单核细胞/巨噬细胞前体细胞（BMSCs）在重组NF-κ B B配体受体激活剂/巨噬细胞集落刺激因子刺激下没有表现出钙离子振荡或分化为多核破骨细胞。IP（3）R2基因敲除的Bcl 3在与成骨细胞共培养或体内无Ca 2+振荡的条件下，可发生破骨细胞生成。此外，我们发现，钙振荡独立的破骨细胞生成不敏感FK 506，钙调磷酸酶抑制剂。两者合计，我们得出结论，这两个Ca 2+振荡/钙调神经磷酸酶依赖性和非依赖性信号通路有助于NFATc 1激活，导致有效的破骨细胞在体内。
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 (IP(3)R2) did not exhibit Ca2+ oscillation or differentiation into multinuclear osteoclasts in response to recombinant receptor activator of NF-kappa B 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 Ca2+ oscillation. Furthermore, we found that Ca2+ oscillation-independent osteoclastogenesis was insensitive to FK506, a calcineurin inhibitor. Taken together, we conclude that both Ca2+ oscillation/calcineurin-dependent and -independent signaling pathways contribute to NFATc1 activation, leading to efficient osteoclastogenesis in vivo.