Novel Signaling Pathways and Therapeutic Targets in Osteoclasts

  • Hiroshi Takayanagi
Part of the Advances in Experimental Medicine and Biology book series (volume 602)

Osteoclasts are multinucleated cells of monocyte/macrophage origin that degrade bone matrix. Their differentiation is mainly dependent on a TNF family cytokine, receptor activator of nuclear factor (NF)-κB ligand (RANKL), and is also under extensive control by a variety of immunomodulatory molecules (Theill, Boyle, and Penninger 2002; Takayanagi 2005; Sato, and Takayanagi 2006). Therefore, osteoclast biology has been in the forefront of osteoimmunology since the very beginning (Arron and Choi 2000; Takayanagi, et al. 2000b). Congenital lack of osteoclasts causes osteopetrosis, which provided insights into essential molecules for osteoclastogenesis including TRAF6, NF-κB and c-Fos (Teitelbaum, and Ross 2003). In addition, genomewide screening techniques shed light on an hitherto unknown set of genes such as nuclear factor of activated T cells (NFAT) c1 ( Takayanagi, et al. 2002a). It is of great importance to understand the sequential molecular events mediated by such essential molecules (TRAF6, NF-κB, c-Fos and NFATc1) in the context of RANKL signaling during osteoclast differentiation. Furthermore, an increasing number of molecules are known to regulate RANKL-mediated osteoclast differentiation. These studies do have not only scientific but also clinical significance, providing novel therapeutic targets in osteoimmunological diseases.


Osteoclast Differentiation Bone Homeostasis Essential Molecule Tumor Necrosis Factor Receptor Family RANKL Signaling 
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© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Hiroshi Takayanagi
    • 1
  1. 1.Department of Cell Signaling Graduate SchoolTokyo Medical and Dental UniversityBunkyo-kuJapan

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