| http://purl.uniprot.org/citations/26046462 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26046462 | http://www.w3.org/2000/01/rdf-schema#comment | "Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are found in a somatic mosaic fashion in patients with multiple enchondromas. Enchondromas are benign cartilaginous tumors arising in the medulla of bone. The mutant IDH1/2 causes elevated levels of D-2-hydroxyglutarate (D-2-HG). Mesenchymal stem cells (MSC) are the precursor of the osteoblastic, chondrogenic and adipocytic lineage and we hypothesized that increased levels of D-2-HG cause multiple enchondromas by affecting differentiation of MSCs. Bone marrow derived MSCs from different donors were differentiated towards osteoblastic, chondrogenic and adipocytic lineage in the presence or absence of 5 mM D-2-HG. Three of four MSCs showed near complete inhibition of calcification after 3 weeks under osteogenic differentiation conditions in the presence of D-2-HG, indicating a block in osteogenic differentiation. Two of four MSCs showed an increase in differentiation towards the chondrogenic lineage. To evaluate the effect of D-2-HG in vivo we monitored bone development in zebrafish, which revealed an impaired development of vertebrate rings in the presence of D-2-HG compared to control conditions (p-value < 0.0001). Our data indicate that increased levels of D-2-HG promote chondrogenic over osteogenic differentiation. Thus, mutations in IDH1/2 lead to a local block in osteogenic differentiation during skeletogenesis causing the development of benign cartilaginous tumors."xsd:string |
| http://purl.uniprot.org/citations/26046462 | http://purl.org/dc/terms/identifier | "doi:10.18632/oncotarget.4024"xsd:string |
| http://purl.uniprot.org/citations/26046462 | http://purl.uniprot.org/core/author | "Baelde H.J."xsd:string |
| http://purl.uniprot.org/citations/26046462 | http://purl.uniprot.org/core/author | "Roelofs H."xsd:string |
| http://purl.uniprot.org/citations/26046462 | http://purl.uniprot.org/core/author | "Bovee J.V."xsd:string |
| http://purl.uniprot.org/citations/26046462 | http://purl.uniprot.org/core/author | "Cleton-Jansen A.M."xsd:string |
| http://purl.uniprot.org/citations/26046462 | http://purl.uniprot.org/core/author | "Suijker J."xsd:string |
| http://purl.uniprot.org/citations/26046462 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26046462 | http://purl.uniprot.org/core/name | "Oncotarget"xsd:string |
| http://purl.uniprot.org/citations/26046462 | http://purl.uniprot.org/core/pages | "14832-14842"xsd:string |
| http://purl.uniprot.org/citations/26046462 | http://purl.uniprot.org/core/title | "The oncometabolite D-2-hydroxyglutarate induced by mutant IDH1 or -2 blocks osteoblast differentiation in vitro and in vivo."xsd:string |
| http://purl.uniprot.org/citations/26046462 | http://purl.uniprot.org/core/volume | "6"xsd:string |
| http://purl.uniprot.org/citations/26046462 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26046462 |
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