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Simple and effective osteoinductive gene therapy by local injection of a bone morphogenetic protein-2-expressing recombinant adenoviral vector and FK506 mixture in rats

Gene Therapy volume 11, pages 439–447 (2004)Cite this article

Abstract

We have previously utilized a human bone morphogenetic protein-2 (BMP-2)-expressing recombinant adenoviral vector (AxCAOBMP-2) for osteoinductive gene therapy in rats. However, immunosuppression is essential for osteoinduction by AxCAOBMP-2 and this is one of the major impediments to its clinical use. Injection of AxCAOBMP-2 together with the immunosuppressant FK506 made it possible to markedly reduce the dose of the immunosuppressive agent and still induce ectopic bone reliably. We injected AxCAOBMP-2 and FK506 into the right calf muscle of rats, while the same number of plaque forming units of AxCAOBMP-2 and the same dose of FK506 placebo (vehicle) were injected into the left calf muscle. At 1, 3, 5, 7, 9 days after injection, BMP-2 mRNA expression was significantly higher in the right calf muscle than in the left calf muscle. At 21 days after injection, significantly more ectopic bone was observed in the right calf muscle than in the left calf muscle. These results indicate that coinjection of FK506 significantly promotes osteoinduction. In addition, local injection of FK506 may also make it possible to prevent a decrease of gene expression with other adenoviral vector.

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Acknowledgements

This work was supported in part by Grants-in-Aid for Scientific Research B (no. 15390612) from the Japanese Ministry of Education, Science, Sports and Culture

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan

    S Kaihara, K Bessho, Y Okubo, J Sonobe, M Kawai & T Iizuka

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  1. S Kaihara
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  2. K Bessho
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  3. Y Okubo
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  4. J Sonobe
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Kaihara, S., Bessho, K., Okubo, Y. et al. Simple and effective osteoinductive gene therapy by local injection of a bone morphogenetic protein-2-expressing recombinant adenoviral vector and FK506 mixture in rats. Gene Ther 11, 439–447 (2004). https://doi.org/10.1038/sj.gt.3302176

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