Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Increased bone formation in osteocalcin-deficient mice


VERTEBRATES constantly remodel bone. The resorption of preexisting bone by osteoclasts and the formation of new bone by osteoblasts is strictly coordinated to maintain bone mass within defined limits. A few molecular determinants of bone remodelling that affect osteoclast activity1–3 have been characterized, but the molecular determinants of osteoblast activity are unknown. To investigate the role of osteocalcin, the most abundant osteoblast-specific non-collagenous protein4, we have generated osteocalcin-deficient mice. These mice develop a phenotype marked by higher bone mass and bones of improved functional quality. Histomorphometric studies done before and after ovariectomy showed that the absence of osteocalcin leads to an increase in bone formation without impairing bone resorption. To our knowledge, this study provides the first evidence that osteocalcin is a determinant of bone formation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others


  1. Soriano, P., Montgomery, C., Geske, R. & Bradley, A. Cell 64, 693–702 (1991).

    Article  CAS  Google Scholar 

  2. Wang, Z-Q. et al. Nature 360, 741–745 (1992).

    Article  ADS  CAS  Google Scholar 

  3. Grigoriadis, A. E. et al. Science 266, 443–448 (1994).

    Article  ADS  CAS  Google Scholar 

  4. Hauschka, P., Lian, J., Cole, D. & Gundberg, C. Physiol. Rev. 69, 990–1047 (1989).

    Article  CAS  Google Scholar 

  5. Weinreb, M., Shinar, D. & Rodan, G. A. J. Bone Miner. Res. 5, 831–842 (1990).

    Article  CAS  Google Scholar 

  6. Boivin, G. et al. Virchows Arch. A. Path. Anat. 417, 505–512 (1990).

    Article  CAS  Google Scholar 

  7. Desbois, C., Hogue, D. A. & Karsenty, G. J. biol. Chem. 269, 1183–1190 (1994).

    CAS  PubMed  Google Scholar 

  8. Bonadio, F. et al. Proc. natn. Acad. Sci. U.S.A. 87, 7145–7149 (1990).

    Article  ADS  CAS  Google Scholar 

  9. Poli, V. et al. EMBO J. 13, 1189–1196 (1994).

    Article  CAS  Google Scholar 

  10. Parfitt, A. M. et al. J. Bone Miner. Res. 2, 595–610 (1987).

    Article  CAS  Google Scholar 

  11. Parfitt, A. M. et al. J. Clin. Invest. 72, 1396–1409 (1983).

    Article  CAS  Google Scholar 

  12. Parfitt, A. M., Riggs, B. L. & Melton, L. J. Osteoporosis: Etiology, Diagnosis and Management. (eds Parfitt, A. M., Riggs, B. L. & Melton, L J.) 501 (Raven, New York, 1988).

    Google Scholar 

  13. Bain, S. D., Bailey, M. C., Celino, D. L., Lantry, M. M. & Edwards, M. W. J. Bone Miner. Res. 8, 435–442 (1993).

    Article  CAS  Google Scholar 

  14. Stitt, T. N. et al. Cell 80, 661–670 (1995).

    Article  CAS  Google Scholar 

  15. Coughlin, S. Thromb. Haemost. 70, 184–187 (1993).

    Article  CAS  Google Scholar 

  16. McMahon, A. P. & Bradley, A. Cell 62, 1073–1085 (1990).

    Article  CAS  Google Scholar 

  17. Luo, G., D'Souza, R., Hogue, D. & Karsenty, G. J. Bone Miner. Res. 10, 325–334 (1995).

    Article  CAS  Google Scholar 

  18. Oldberg, A., Franzen, A. & Heinegard, D. Proc. natn. Acad. Sci. U.S.A. 83, 8819–8823 (1986).

    Article  ADS  CAS  Google Scholar 

  19. Ramirez-Solis, R., Davis, A. & Bradley, A. Meth. Enzym. 225, 855–878 (1993).

    Article  CAS  Google Scholar 

  20. Bradley, A. Teratocarcinomas and Embryonic Stem Cells: A Practical Approach (ed. Robinson, E. J.) 113–151 (IRL, Oxford, 1987).

    Google Scholar 

  21. Gundberg, C., Hauschka, P., Lian, J. & Gallop, P. M. Meth. Enzym. 107, 516–566 (1984).

    Article  CAS  Google Scholar 

  22. Vignery, A. & Baron, R. Anat. Rec. 196, 191–200 (1980).

    Article  CAS  Google Scholar 

  23. Andersson, G. N. & Marks, S. J. J. Histochem. Cytochem. 37, 115–117 (1989).

    Article  CAS  Google Scholar 

  24. Boyce, B. F., Yoneda, T., Lowe, C., Soriano, P. & Mundy, G. R. J. Clin. Invest. 90, 1622–1627 (1992).

    Article  CAS  Google Scholar 

  25. Jilka, R. L. et al. Science 257, 88–91 (1992).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

Reprints and permissions

About this article

Cite this article

Ducy, P., Desbois, C., Boyce, B. et al. Increased bone formation in osteocalcin-deficient mice. Nature 382, 448–452 (1996).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing