| Project/Area Number |
17390530
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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 |
Surgical dentistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MORI Yoshiyuki The University of Tokyo, Faculty of Medicine, Lecturer (70251296)
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| Co-Investigator(Kenkyū-buntansha) |
TAKATO Tsuyoshi The University of Tokyo, Faculty of Medicine, Professor (90171454)
CHUNG Ung-il The University of Tokyo, Faculty of Engineering, Professor (30345053)
FUJIHARA Hisako The University of Tokyo, Faculty of Medicine, Clinical Fellow (80396746)
OHKUBO Kazumi The University of Tokyo, Faculty of Medicine, Assistant Professor (10396715)
KAWAGUCHI Hiroshi The University of Tokyo, Faculty of Medicine, Assistant Professor (40282660)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥15,840,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2007: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2006: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2005: ¥7,100,000 (Direct Cost: ¥7,100,000)
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| Keywords | bone formation / differentiation signal / fibroblasts / gene transfer |
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| Research Abstract |
The present study aimed to develop a basic technology for bone regeneration using fibroblasts, particularly focusing on differentiation signal and cell sources. The present study has four major findings.
1. Development of a screening system for osteoblast differentiation: We utilized a transgene expressing Green Fluorescence Protein (GFP) driven by the 2.3 kb fragment of type I collage promoter (Col1GFP). Cells containing the transgene fluoresce upon osteoblast differentiation. Embryonic stem (ES) cells were isolated from Col1GFP transgenic mice (Col1GFP-ES cells). Using Col1GFP-EScells as a cell-based sensor for osteoblast differentiation, we were able to monitor the differentiation easily, precisely and non-invasively.
2. Identification of the minimal and sufficient signaling unit for bone formation: Using Col1GFP system, we comprehensively screened ostegenic signals. Through the screening, the combination of BMP signaling and Runx2 was identified as the minimal and sufficient signaling unit for osteoblast differentiation. Molecular mechanisms underlying the osteogenic induction by the combination were also clarified.
3. Achievement of bone regeneration using skin fibroblasts: Transplantation of skin fibroblasts, in which BMP signaling and Runx2 were activated, induced bone regeneration in animal bone defect model.
4. Establishment of isolation and culture method of human fibroblasts for bone regeneration: Human fibroblasts differentiated into osteoblastic cells in vitro when BMP signaling and Runx2 were activated in those cells.
Considering these findings, we think that the original objective of the present study is accomplished. However, our current system depends on gene transfer using viral vectors, which may be a crucial hurdle in its application to clinical settings; we are planning to use biocompatible gene carriers or osteogenic small compounds as surrogates for viral vectors.
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