文章基本信息

标题：Osteoblasts induce Ca2+ oscillation-independent NFATc1 activation during osteoclastogenesis
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作者：Yukiko Kuroda ; Chihiro Hisatsune ; Takeshi Nakamura 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2008
卷号：105
期号：25
页码：8643-8648
DOI：10.1073/pnas.0800642105
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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-{kappa}B 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 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.
关键词：differentiation ; inositol 1,4,5-trisphosphate receptor (IP3R) ; osteoclast ; receptor activator of NF-κB ligand (RANKL) ; calcium