| Project/Area Number |
07457335
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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 | Shinshu University |
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Principal Investigator |
EBARA Sohei Shinshu Univ.Dept of Orthopaedic Surgery, Associate Professor, 医学部附属病院, 講師 (40176780)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAOKA Kunio Shinshu Univ.Dept of Orthopaedic Surgery, Professor and Chairman, 医学部, 教授 (30112048)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | chondrocyte / osteoblast / bone morphogenetic protein / E-box / Helix-loop-helix / mechanical loading / shear stress responsive element / northern blotting / ノーザンブロッティング / 破骨細胞 / 基質接着構造 / 細胞内情報伝達系 / 初期応答遺伝子 / チロシンキナーゼ / プロティンキナーゼC / Cキナーゼ |
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| Research Abstract |
Chondrocytes, Osteoblasts, bone marrow cells and undifferentiated mesenchymal cells response to mechanical stimulation through their gene-expression. Bone morphogenetic protein-4(BMP-4) is a member of transforming growth factor type beta (TGF-beta) superfamily and plays a critical role in cartilage and bone formation. To understand how the expression of BMP-4 is regulated, it is essential to analyze the promoter. We analyzed the promoter activity of murine bone morphogenetic protein-4 (mBMP-4), especially with a focus on the 5'-flanking region of exon I.The promoter region of the mBMP-4 gene consists of three domains. The first domain is the region from -265 to the transcriptional start site, the second domain extends from -690 to -266 and the third from -1508 to -689, within this 1753-bp region. The first and the third domains showed positive transcriptional activity while the second domain behaved as a negative regulator. These findings suggest that transcriptional regulation of the mBMP-4 gene is a finely balanced process involving multiple cis-acting DNA domains. In the 5' flanking region of mBMP-4 gene, shear stress responsive element (SSRE) exist around-1550bp of exon I.We are now under investigation of the mechanical effect on mBMP-4 and osteogenic gene expression. Northern blotting showed no reactive change of BMP-4 expression to mechanical loading in MC3T3E1 cell. Using other cell lines, we are examining the reactive response of BMP-4 and other osteoblastic proteins to mechanical loading.
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