2002 Fiscal Year Final Research Report Summary
Bone Induction by Human Bone Morphogenetic Protein Expressing Adenoviral Vector
| Project/Area Number |
12307048
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
IIZUKA Tadahiko Kyoto University, Oral and Maxillofacial Surgery, Professor, 医学研究科, 教授 (80026921)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Kazuya Kyoto University, Oral and Maxillofacial Surgery, Assistant Professor, 医学研究科, 助手 (90263087)
BESSHO Kazuuhisa Kyoto University, Oral and Maxillofacial Surgery, Assistant Professor, 医学研究科, 助手 (90229138)
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| Project Period (FY) |
2000 – 2002
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| Keywords | bone morphogenetic protein / cytokine / gene transfer / adenovirus / vector / bone injection / immunosuppression / infection |
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| Research Abstract |
Large quantity of bone morphogenetic protein (BMP) is required with primates to get the bone induction for which to become stable when BMP is used under the condition of the protein. This is a big problem for clinical application. There is a possibility to solve this problem by using the BMP gene transfer method with an adenoviral vector because the infection efficiency of the adenovirus is especially high with primates.
We constructed a human bone morphogenetic protein-2 (BMP-2)-expressing adenoviral vector. C2C12 cells were infected in vitro with the vital vector. An efficient gene transfer to the C2C12 and BMP-2 expression in the cells infected with the viral vector were confirmed. C2C12 cells transfected with the BMP-2 gene by the vector showed intracellular accumulation alkaline phosphatase, and also produced and secreted osteocalcim into the culture medium, demonstrating that in vitro transfer of the BMP-2 gene to these cells had caused the transformation of myoblasts to the osteo
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blast lineage. Then we examined the effectiveness of BMP-2 gene transfer by the viral vector in vivo. Osteoinduction was seen in muscle when the viral vector was injected immunosuppression. We also evaluated the time course of osteoinduction by the viral vector in immunocompetent and immunosuppressed rats. In vivo bone formation at 14 and 21 days after injection was only seen in the immunosuppressed rats, while most of the cells infected with the viral vector were eliminated by the host immune system soon after injection in the immunocompetent rats. Therefore, we evaluated osteoinduction by the viral vector using biomaterial (atelopeptide collagen) to mask the immune response or local application of immunosuppressant in immunocompetent rats.
Our results suggested that gene therapy with the BMP-2-expressing adenoviral vector could be performed under transient immunosuppression, with local application of immunosuppressant, or with effective masking of the host immune response and may be useful for bone reconstruction. Less
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