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Vitamin D Action and Regulation of Bone Remodeling: Suppression of Osteoclastogenesis by the Mature Osteoblast†‡

  1. Paul A Baldock1,2,*,
  2. Gethin P Thomas1,2,3,
  3. Jason M Hodge4,
  4. Sara UK Baker1,
  5. Uwe Dressel5,
  6. Peter D O'Loughlin6,
  7. Geoffrey C Nicholson4,
  8. Kathy H Briffa1,7,
  9. John A Eisman1,
  10. Edith M Gardiner1,5

Article first published online: 17 JUL 2006

DOI: 10.1359/jbmr.060714

Issue

Journal of Bone and Mineral Research

Journal of Bone and Mineral Research

Volume 21, Issue 10, pages 1618–1626, October 2006

Additional Information

How to Cite

Baldock, P. A., Thomas, G. P., Hodge, J. M., Baker, S. U., Dressel, U., O'Loughlin, P. D., Nicholson, G. C., Briffa, K. H., Eisman, J. A. and Gardiner, E. M. (2006), Vitamin D Action and Regulation of Bone Remodeling: Suppression of Osteoclastogenesis by the Mature Osteoblast. J Bone Miner Res, 21: 1618–1626. doi: 10.1359/jbmr.060714

Author Information

  1. 1

    Bone Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, New South Wales, Australia

  2. 2

    Bone Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, New South Wales, Australia

  3. 3

    Current address: Centre for Immunology and Cancer Research, University of Queensland, Brisbane, Queensland, Australia

  4. 4

    Department of Clinical and Biomedical Sciences, The University of Melbourne, Geelong, Victoria, Australia

  5. 5

    Current address: School of Medicine, University of Queensland, Brisbane, Queensland, Australia

  6. 6

    Department of Clinical Biochemistry, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia

  7. 7

    Current address: Curtin University of Technology, Perth, Australia

*Paul A Baldock, PhD Garvan Institute of Medical Research 384 Victoria Street Darlinghurst, Sydney, NSW 2010, Australia

  1. †

    Dr Eisman receives research funding from and/or has provided consultation to Amgen, deCode, Eli Lilly & Co., GE-Lunar, Merck Sharp & Dohme, Novartis, Organon, Pfizer, Roche-GSK, Sanofi-Aventis, and Servier. All other authors state that they have no conflicts of interest.

  2. ‡

    Published online on July 17, 2006;

Publication History

  1. Issue published online: 4 DEC 2009
  2. Article first published online: 17 JUL 2006
  3. Manuscript Accepted: 12 JUL 2006
  4. Manuscript Revised: 11 APR 2006
  5. Manuscript Received: 13 DEC 2005

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Keywords:

  • vitamin D;
  • osteoclastogenesis;
  • mature osteoblast;
  • osteoprotegerin

Abstract

Vitamin D acts through the immature osteoblast to stimulate osteoclastogenesis. Transgenic elevation of VDR in mature osteoblasts was found to inhibit osteoclastogenesis associated with an altered OPG response. This inhibition was confined to cancellous bone. This study indicates that vitamin D–mediated osteoclastogenesis is regulated locally by OPG production in the mature osteoblast.

Introduction: Vitamin D stimulates osteoclastogenesis acting through its nuclear receptor (VDR) in immature osteoblast/stromal cells. This mobilization of calcium stores does not occur in a random manner, with bone preferentially removed from cancellous bone. The process whereby the systemic, humoral regulator is targeted to a particular region of the skeleton is unclear.

Materials and Methods: Bone resorption was assessed in mice with vitamin D receptor transgenically elevated in mature osteoblasts (OSVDR). Vitamin D–mediated osteoclastogenesis was examined in vitro using OSVDR osteoblasts and osteoblastic RANKL: osteoprotegerin (OPG) examined in vivo and in vitro after vitamin D treatment.

Results: Vitamin D–mediated osteoclastogenesis was reduced in OSVDR mice on chow and calcium-restricted diets, with effects confined to cancellous bone. OSVDR osteoblasts had a reduced capacity to support osteoclastogenesis in culture. The vitamin D–mediated reduction in OPG expression was reduced in OSVDR osteoblasts in vivo and in vitro, resulting in a reduced RANKL/OPG ratio in OSVDR compared with wildtype, after exposure to vitamin D.

Conclusions: Mature osteoblasts play an inhibitory role in bone resorption, with active vitamin D metabolites acting through the VDR to increase OPG. This inhibition is less active in cancellous bone, effectively targeting this region for resorption after the systemic release of activated vitamin D metabolites.

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