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Regulatory Mechanisms of RANKL Presentation to Osteoclast Precursors

  • Skeletal Biology and Regulation (MR Forwood and A Robling, Section Editors)
  • Published:
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Abstract

It is important to understand the molecular mechanisms regulating osteoclast formation, as excess activation of osteoclasts is associated with various osteopenic disorders. Receptor activator of nuclear factor kappa B (RANKL) is a central player in osteoclastogenesis. Recent findings suggest that osteocytes are the major supplier of RANKL to osteoclast precursors. It has also been suggested that osteocyte cell death upregulates the RANKL/osteoprotegerin (OPG) ratio in viable osteocytes adjacent to apoptotic osteocytes in areas of bone microdamage, thus, contributing to localized osteoclast formation. Indeed, viable osteocytes can provide RANKL through direct interactions with osteoclast precursors at osteocyte dendritic processes. In addition, OPG tightly regulates RANKL cell surface presentation in osteocytes, which contributes to the inhibition of RANKL signaling, as well as the decoy receptor function of OPG. By contrast, the physiological role of RANKL in osteoblasts is yet to be clarified, although similar mechanisms of regulation are observed in both osteocytes and osteoblasts.

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Conflict of Interest

M. Honma has received research support from Grant-in-Aid for Scientific Research (B) 24390349 from the Japan Society for the Promotion of Science. Y. Ikebuchi has received research support from Grant-in-Aid for Challenging Exploratory Research 25670632 from the Japan Society for the Promotion of Science. Y. Kariya has received research support from Grant-in-Aid for Young Scientists (Start-up) 24890048 from the Japan Society for the Promotion of Science. H Suzuki declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

All studies by M. Honma, Y. Ikebuchi, Y. Kariya and H. Suzuki involving animal subjects were performed after approval of the Institutional Animal Care and Use Committee of Graduate School of Medicine, the University of Tokyo.

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Authors and Affiliations

  1. Department of Pharmacy, the University of Tokyo Hospital, Faculty of Medicine, the University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Masashi Honma, Yuki Ikebuchi, Yoshiaki Kariya & Hiroshi Suzuki

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  1. Masashi Honma
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  2. Yuki Ikebuchi
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  3. Yoshiaki Kariya
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  4. Hiroshi Suzuki
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Correspondence to Masashi Honma.

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Honma, M., Ikebuchi, Y., Kariya, Y. et al. Regulatory Mechanisms of RANKL Presentation to Osteoclast Precursors. Curr Osteoporos Rep 12, 115–120 (2014). https://doi.org/10.1007/s11914-014-0189-0

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  • DOI: https://doi.org/10.1007/s11914-014-0189-0

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