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Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat

Gene Therapy volume 10, pages 1735–1743 (2003)Cite this article

Abstract

Bone morphogenetic protein (BMP) adenoviral vectors for the induction of osteogenesis are being developed for the treatment of bone pathology. However, it is still unknown which BMP adenoviral vector has the highest potential to stimulate bone formation in vivo. In this study, the osteogenic activities of recombinant human BMP-2, BMP-4, BMP-6, BMP-7, and BMP-9 adenoviruses were compared in vitro, in athymic nude rats, and in Sprague–Dawley rats. In vitro osteogenic activity was assessed by measuring the alkaline phosphatase activity in C2C12 cells transduced by the various BMP vectors. The alkaline phosphatase activity induced by 2 × 105 PFU/well of BMP viral vector was 4890 × 10−12 U/well for ADCMVBMP-9, 302 × 10−12 U/well for ADCMVBMP-4, 220 × 10−12 U/well for ADCMVBMP-6, 45 × 10−12 U/well for ADCMVBMP-2, and 0.43 × 10−12 U/well for ADCMVBMP-7. The average volume of new bone induced by 107 PFU of BMP vector in athymic nude rats was 0.37±0.03 cm3 for ADCMVBMP-2, 0.89±0.07 cm3 for ADCMVBMP-4, 1.02±0.07 cm3 for ADCMVBMP-6, 0.24±0.05 cm3 for ADCMVBMP-7, and 0.63±0.07 cm3 for ADCMVBMP-9. In immunocompetent Sprague–Dawley rats, no bone formation was demonstrated in the ADCMVBMP-2, ADCMVBMP-4, and ADCMVBMP-7 groups. ADCMVBMP-6 at a viral dose of 108 PFU induced 0.10±0.03 cm3 of new bone, whereas ADCMVBMP-9 at a lower viral dose of 107 PFU induced more bone, with an average volume of 0.29±0.01 cm3.

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Acknowledgements

We wish to thank the Genetics Institute for providing some BMP cDNAs, viral vectors, BMP-9 protein, and antibody. This work was supported in part by grants from Medtronic-Sofamor Danek, Inc. and the National Institutes of Health (Grant No. R01 AR46488-01A2, GAH).

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Authors and Affiliations

  1. Department of Neurosurgery, Molecular Neurosurgery Lab, University of Virginia Health System, Charlottesville, VA, USA

    J Z Li, H Li, T Sasaki, D Holman, B Beres, G R Hankins & G A Helm

  2. Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

    R J Dumont

  3. Genetics Institute, Andover, MA, USA

    D D Pittman

  4. Department of Biomedical Engineering, University of Virginia Health System, Charlottesville, VA, USA

    G A Helm

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Li, J., Li, H., Sasaki, T. et al. Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat. Gene Ther 10, 1735–1743 (2003). https://doi.org/10.1038/sj.gt.3302075

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