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Increased bone formation in osteocalcin-deficient mice

Nature volume 382, pages 448–452 (1996)Cite this article

Abstract

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.

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References

  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

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Authors and Affiliations

  1. Department of Molecular Genetics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 45, Houston, Texas, 77030, USA

    Patricia Ducy, Christelle Desbois & Gerard Karsenty

  2. Department of Pathology, The University of Texas Health Science Center, San Antonio, Texas, 78284, USA

    Brendan Boyce & Beryl Story

  3. Department of Medicine, The University of Texas Health Science Center, San Antonio, Texas, 78284, USA

    Colin Dunstan

  4. Department of Basic Science, Dental Branch University of Texas, Houston, Texas, 77030, USA

    Gerald Pinero

  5. Department of Orthopaedics, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA

    Erica Smith & Steven Goldstein

  6. Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA

    Jeffrey Bonadio

  7. Department of Orthopaedics, Yale School of Medicine, New Haven, Connecticut, 06510, USA

    Caren Gundberg

  8. Howard Hughes Medical Institute and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA

    Allan Bradley

Authors
  1. Patricia Ducy
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  2. Christelle Desbois
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  3. Brendan Boyce
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  4. Gerald Pinero
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  5. Beryl Story
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  6. Colin Dunstan
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  8. Jeffrey Bonadio
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  10. Caren Gundberg
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  11. Allan Bradley
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  12. Gerard Karsenty
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Ducy, P., Desbois, C., Boyce, B. et al. Increased bone formation in osteocalcin-deficient mice. Nature 382, 448–452 (1996). https://doi.org/10.1038/382448a0

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