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2014 Fiscal Year Final Research Report

The research on the contribution of mutant IDH gene to the formation of cartilagenous tumors

Research Project

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Project/Area Number 25670642
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Orthopaedic surgery
Research InstitutionKyoto University

Principal Investigator

OKAMOTO Takeshi  京都大学, 医学(系)研究科(研究院), 講師 (30414113)

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)
Project Period (FY) 2013-04-01 – 2015-03-31
Keywordsoncometabolite / 軟骨形成腫瘍 / isocitrate dehydorgenase
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.

Free Research Field

骨軟部腫瘍

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Published: 2016-06-03  

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