| Project/Area Number |
25670642
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Kyoto University |
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Principal Investigator |
OKAMOTO Takeshi 京都大学, 医学(系)研究科(研究院), 講師 (30414113)
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| Co-Investigator(Kenkyū-buntansha) |
JIN Younghui 京都大学, 再生医科学研究所, 研究員 (90620344)
TOGUCHIDA Junya 京都大学, 再生医科学研究所, 教授 (40273502)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | oncometabolite / 軟骨形成腫瘍 / isocitrate dehydorgenase / イソクエン酸デヒドロゲナーゼ / 遺伝子変異 / 人工多能性幹細胞 / エピゲノム解析 / トランスクリプトーム解析 |
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| Outline of Final Research Achievements |
The incidence of IDH mutations was previously shown to be detected in cartilageneous tumors, whereas they have rarely been found in other mesenchymal tumors. To address this unique tumor specificity, we examined the effects of IDH1 R132C gene into human mesenchymal stem cells(hMSC). The induction of the IDH1 R132C into hMSC markedly increased the amound of 2-HG and global histone methylation. The induction of IDH1 R132C promoted the chondrogenic differentiation of hMSC by enhancing the expression of SOX9 and COL2A1 genes in association with an increase in the active mark (H3K4me3), but dusrupted cartilage matrix formation. On the other hand, IDH1 R132C inhibited expression of the ALP gene, and subsequently inhibited osteogenic differentiation in hMSC and also in human osteosarcoma cells. These results suggested that IDH1 R132C contributed to the formation of cartilagenous tumors by dysregulating the chondrogenic and osteogenic differentiation via gene-specific histone modulation.
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