Project/Area Number |
12470437
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Surgical dentistry
|
Research Institution | KYOTO UNIVERSITY |
Principal Investigator |
BESSHO Kazuuhisa Kyoto University, Oral and Maxillofacial Surgery, Assistant Professor, 医学研究科, 助手 (90229138)
|
Co-Investigator(Kenkyū-buntansha) |
IIZUKA Tadahiko Kyoto University, Oral and Maxillofacial Surgery, Professor, 医学研究科, 教授 (80026921)
|
Project Period (FY) |
2000 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥15,800,000 (Direct Cost: ¥15,800,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥10,400,000 (Direct Cost: ¥10,400,000)
|
Keywords | bone morphogenetic protein / cytokine / recombinant / purification / Escherichia Coli / bone induction / gene transfer / bioassay / 遺伝子組み換え / 骨形成 |
Research Abstract |
At present, several recombinant human bone morphogenetic proteins (rhBMPs) can be produced in mammalian cells, such as Chinese hamster ovary (CHO) cells. If rhBMPs with a high activity could be produced in bacteria, the bacterial expression system is invaluable, as it is possible to produce a large quantity of rhBMPs at low-cost. We examined the bone-inducing ability of Escherichia coli-derived rhBMP-2 (ErhBMP-2) and compared it with that of CHO cell-derived rhBMP-2 (CrhBMP-2) using bioassays. Quantitative analysis indicated that the activity of ErhBMP-2 was higher than that of CrhBMP-2, so ErhBMP-2 may be useful for inducing bone formation. Furthermore, we evaluated the effects of hyperbaric oxygenation (HBO), fibroblast growth factor-2 (FGF-2) and elcatonin on bone formation by ErhBMP-2. These results showed that each therapy is effective in enhancing osteoinduction. Then we examined the effectiveness of BMP-2 gene transfer by the viral vector in vivo. Osteoinduction was seen when the viral vector was injected immunosuppression. Therefore, we evaluated osteoinduction by the viral vector using atelopeptide collagen to mask the immune response or local application of immunosappressant in immunocompetent rats Our results suggested that ErhBMP-2 and gene therapy with the BMP-2-expressing adenoviral vector may be useful for bone reconstruction.
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