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Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery

Gene Therapy volume 11, pages 1312–1320 (2004)Cite this article

Abstract

Efficacious bone regeneration could revolutionize the clinical management of bone and musculoskeletal disorders. Although several bone morphogenetic proteins (BMPs) (mostly BMP-2 and BMP-7) have been shown to induce bone formation, it is unclear whether the currently used BMPs represent the most osteogenic ones. Until recently, comprehensive analysis of osteogenic activity of all BMPs has been hampered by the fact that recombinant proteins are either not biologically active or not available for all BMPs. In this study, we used recombinant adenoviruses expressing the 14 types of BMPs (AdBMPs), and demonstrated that, in addition to currently used BMP-2 and BMP-7, BMP-6 and BMP-9 effectively induced orthotopic ossification when either AdBMP-transduced osteoblast progenitors or the viral vectors were injected into the quadriceps of athymic mice. Radiographic and histological evaluation demonstrated that BMP-6 and BMP-9 induced the most robust and mature ossification at multiple time points. BMP-3, a negative regulator of bone formation, was shown to effectively inhibit orthotopic ossification induced by BMP-2, BMP-6, and BMP-7. However, BMP-3 exerted no inhibitory effect on BMP-9-induced bone formation, suggesting that BMP-9 may transduce osteogenic signaling differently. Our findings suggest that BMP-6 and BMP-9 may represent more effective osteogenic factors for bone regeneration.

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Acknowledgements

We thank Dr Mark Bolander of Mayo Clinic for valuable discussion and critical review of the manuscript. We thank the Genetics Institute of Cambridge, MA, for providing human BMP cDNAs. We apologize to the researchers whose original work was not cited due to space constraints. The work was supported in part by research grants from the Aircast Foundation, the Brinson Foundation, North American Spine Society, and the Orthopaedic Research and Education Foundation. Q Kang was a recipient of an International Postdoctoral Fellowship from the National Institutes of Health (F05 AT002014-01).

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Author notes

  1. A T Deyrup

    Present address: Department of Pathology, Emory University, Atlanta, GA, USA

  2. Q Kang, M H Sun and H Cheng: QK, MHS, and HC Contributed equally to this work

Authors and Affiliations

  1. Department of Surgery, Molecular Oncology Laboratory, The University of Chicago Medical Center, Chicago, IL, USA

    Q Kang, M H Sun, H Cheng, Y Peng, A G Montag, A T Deyrup, W Jiang, H H Luu, J Luo, J P Szatkowski, P Vanichakarn, J Y Park, Y Li, R C Haydon & T-C He

  2. The Children's Hospital of Chongqing University of Medical Sciences, Chongqing, China

    Q Kang

  3. Committee on Genetics, The University of Chicago, Chicago, IL, USA

    Y Peng & T-C He

  4. Department of Pathology, The University of Chicago, Chicago, IL, USA

    A G Montag & A T Deyrup

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Kang, Q., Sun, M., Cheng, H. et al. Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery. Gene Ther 11, 1312–1320 (2004). https://doi.org/10.1038/sj.gt.3302298

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