| Project/Area Number |
10671360
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Osaka University |
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Principal Investigator |
YASUI Natsuo Osaka University Medical School, Associate Professor, 医学系研究科, 助教授 (00157984)
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| Co-Investigator(Kenkyū-buntansha) |
NAKATA Ken Osaka University Medical School, Assistant Professor, 医学系研究科, 助手 (00283747)
NAKASE Takanobu Osaka University Medical School, Assistant Professor, 医学系研究科, 助手 (00283755)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Distraction Osteogenesis / Mechanical stress / Bone formation / BMP / 内軟骨性骨化 / 膜性骨化 / 類軟骨性骨化 |
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| Research Abstract |
Bone lengthening with osteotomy and gradual distraction was achieved in 57 rats and the effect of mechanical tension-stress on gene expression of bone morphogenetic proteins (BMPs) was investigated by in situ hybridization and northern blot analysis using probes of BMP-2, -4, -6, -7, and GDF-5. There was a lag phase for 7 days after femoral osteotomy until gradual distraction was carried out for 21 days at a rate of 0.25 mm/12 h using a small external fixator. As distraction was started, the callus were elongated and eventually separated into proximal and distal segments forming a fibrous interzone in the middle. Expression of BMP-2 and BMP-4 mRNA was dramatically induced at this stage. Their signals were detected widely among chondrogenic and osteogenic cells and their precursor cells sustaining mechanical tension-stress at the fibrous interzone. BMP-6 and GDF-5 mRNAs were detected exclusively in chondrogenic cells at the both ends of fibrous interzone, where endochondral ossification occurred. As distraction advanced, the cartilage was progressively resorbed from both ends and new bone was formed directly by intramembranous ossification. The signals of BMP-6 and GDF-5 mRNA declined by this stage, while those of BMP-2 and -4 were maintained in high level as long as distraction was continued. After completion of distraction, the fibrous interzone fused and the lengthened segment was consolidated. None of BMP-2, -4, 6, and GDF-5 was expressed at this stage. The signals of BMP-7 was never detected throughout the experiment. These data suggest that excellent and uninterrupted bone formation during distruction osteogenesis owes to enhanced expression of BMP-2 and BMP-4 genes by mechanical tension-stress. Abundant gene products of BMP-2 and -4 could induce in situ new bone formation by paracrine and autocrine mechanism.
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