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Novel osteoclast signaling mechanisms

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Abstract

Osteoclasts are cells of monocyte/macrophage origin that degrade bone matrix. Receptor activator of NF-κB ligand (RANKL) induces osteoclast differentiation in the presence of macrophage colony-stimulating factor. RANKL activates the tumor necrosis factor receptor-associated factor 6, c-Fos, and calcium signaling pathways, all of which are indispensable for the induction and activation of nuclear factor of activated T cells (NFAT) c1. NFATc1 is the master transcription factor for osteoclast differentiation, which regulates many osteoclast-specific genes. Multiple immunoglobulin-like receptors associated with immunoreceptor tyrosine-based activation motif (ITAM)-harboring adapters, Fc receptor common γ subunit (FcRγ), and DNAX-activating protein (DAP) 12 mediate costimulatory signals for RANK, which activate calcium signaling through phospholipase Cγ (PLCγ). In addition to calcineurin-NFATc1, calcium signaling activates the CaMK-CREB (calcium/calmodulin activated kinase-cyclic AMP-response element binding protein) pathway, which also plays a critical role in osteoclastogenesis. This review summarizes recent advances in the study of signaling mechanisms of osteoclast differentiation.

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Authors and Affiliations

  1. Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University and COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Yushima 1-5-45, Bunkyo-ku, Tokyo, 113-8549, Japan

    Hiroshi Takayanagi MD, PhD

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  1. Masahiro Shinohara PhD
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  2. Hiroshi Takayanagi MD, PhD
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Correspondence to Hiroshi Takayanagi MD, PhD.

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Shinohara, M., Takayanagi, H. Novel osteoclast signaling mechanisms. Curr Osteoporos Rep 5, 67–72 (2007). https://doi.org/10.1007/s11914-007-0005-1

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