| Project/Area Number |
16K20064
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Oita University |
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Principal Investigator |
Mariko Hida 大分大学, 医学部, 客員研究員 (10737224)
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| Research Collaborator |
Matsuo Noritaka
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | コラーゲン / 軟骨 / 転写 / 骨 |
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| Outline of Final Research Achievements |
In this study, we investigated the proximal promoter of Col11a1 and Col27a1 gene in chondrocytes.In Col11a1 gene, cell transfection experiments exhibited the suppression of the promoter activity without NF-Y binding sequence. Luciferase assays exhibited that GC rich sequence is a critical elements. Overexpression of Sp1 was significantly increased, and knockdown of Sp1 was suppressed the expression of endogenous transcript. Taken together, the transcription factor NF-Y and Sp1 upregulates the proximal promoter activity of Col11a1 gene in chondrocytes.In Col27a1 gene, oligo-Capping Race analysis revealed that mouse Col27a1 gene has two alternative promoters in chondrocytes. Transient transfection experiments indicated that the proximal promoter activity was from -586 to -445 in the downstream promoter and was from -310 to +1 in the upstream promoter. However, the mechanism of col27a1 gene regulation in chondrocytes has not been understood in this study.
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| Academic Significance and Societal Importance of the Research Achievements |
申請者らは、活性領域の同定が困難とされていた組織特異的シスエレメントの網羅的スクリーニング法を開発し、これまで報告のない２つの線維性コラーゲン遺伝子の軟骨特異的エンハンサー領域を発見する事ができた。本研究の進展により、軟骨における分子発現機構や軟骨分化メカニズムの解明に貢献するだけでなく、軟骨形成不全症の診断や治療に新知見を与える事ができ、再生医療への応用も期待できる。
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