| Project/Area Number |
15390460
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
JINGUSHI Seiya Kyushu University, Graduate School of Medical Sciences, Associate Professor, 医学研究院, 助教授 (80235829)
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| Co-Investigator(Kenkyū-buntansha) |
OKAZAKI Ken Kyushu University, Graduate School of Medical Sciences, Assistant Professor, 医学研究院, 助手 (10398092)
志田 純一 九州大学, 大学病院, 助手 (90346792)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2003: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Keywords | BMP-2 / Bone graft / Bone induction / βTCP / bisphosphonate / bTCP / Bone graft / BMP / bone induction |
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| Research Abstract |
1)Intramuscular Bone Induction by the Simultaneous Administration of Recombinant Human Bone Morphogenetic Protein 2 and Bisphosphonate for Autobone Graft
This study was conducted to determine whether rhBMP-2-induced bone tissue could be maintained by simultaneous administration of bisphosphonate, and to investigate whether the induced bone could be used for bone grafting. In this study, we first applied rhBMP-2 alone to aβ-TCP disk and inoculated it into rat quadriceps muscle. Bone area and the number of tartrate-resistant acid phosphatase (TRAP)-positive cells in the induced bone disk peaked at 2 weeks, and induced bone resorption occurred later. Bisphosphonate and rhBMP-2 were then simultaneously applied to aβ-TCP disk and inoculated as in the first experiment. The addition of bisphosphonate decreased the number of TRAP-positive cells and increased the bone area and compression strength at 4 weeks. In the last experiment, aβ-TCP disk treated with rhBMP-2 and bisphosphonate was free-gr
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afted to parietal bone 4 weeks after inoculation. Both bone disks united similarly. We concluded that the concurrent use of bisphosphonate prevented bone absorption attributed to osteoclast activity after bone induction by rhBMP-2. The bisphosphonate application did not disturb the union of induced bone to host bone.
2)Scale up of bone tissue by rhBMP-2,and simulation experiment for clinical use
This study was conducted to (1)confirm that when the size of carrier is increased, the induced bone can form the same in the center as well as on the periphery of the carrier; (2)simulate the in vivo banking for vascularized autograft bone. In experiment 1,1 cm diameter sphere of β-TCP was applied with 200 μg rhBMP-2 and 10^<-5> M bisphosphonate (Minodronate). It was then inoculated into the rabbit quadriceps and harvested 5 weeks later (n=3). In experiment 2,β-TCP was generated as 1/3 hollow cylinder with 4-mm outer radius,2-mm inner radius and 10-mm length. After applied with 50 μg rhBMP-2 and 10^<-5> M Minodronate, it was then inoculated into the rat quadriceps. Four weeks later, the induced bone was transplanted as muscle-pedicled flap onto the adjacent femur and harvested after four and eight more weeks (n=3).
In experiment 1,good bone formation was observed at the central as well as peripheral region of the sphere. In experiment 2,good bone formation and bony union to femur at both 4 and 8-week were detected on the x-ray film. The presence of new bone formation around the screw was observed. Transplantation of the β-TCP carrier treated with rhBMP-2 and bisphosphonate into the muscular tissue may have clinical potential for in vivo banking for muscle-pedicled bone flap. Less
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