| http://purl.uniprot.org/citations/20495570 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20495570 | http://www.w3.org/2000/01/rdf-schema#comment | "Chondrocyte hypertrophy followed by cartilage matrix degradation and vascular invasion, characterized by expression of type X collagen (COL10A1), matrix metalloproteinase-13 (MMP-13) and vascular endothelial growth factor (VEGF), respectively, are central steps of endochondral ossification during normal skeletal growth and osteoarthritis development. A COL10A1 promoter assay identified hypoxia-inducible factor-2alpha (HIF-2alpha, encoded by EPAS1) as the most potent transactivator of COL10A1. HIF-2alpha enhanced promoter activities of COL10A1, MMP13 and VEGFA through specific binding to the respective hypoxia-responsive elements. HIF-2alpha, independently of oxygen-dependent hydroxylation, was essential for endochondral ossification of cultured chondrocytes and embryonic skeletal growth in mice. HIF-2alpha expression was higher in osteoarthritic cartilages versus nondiseased cartilages of mice and humans. Epas1-heterozygous deficient mice showed resistance to osteoarthritis development, and a functional single nucleotide polymorphism (SNP) in the human EPAS1 gene was associated with knee osteoarthritis in a Japanese population. The EPAS1 promoter assay identified RELA, a nuclear factor-kappaB (NF-kappaB) family member, as a potent inducer of HIF-2alpha expression. Hence, HIF-2alpha is a central transactivator that targets several crucial genes for endochondral ossification and may represent a therapeutic target for osteoarthritis."xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://purl.org/dc/terms/identifier | "doi:10.1038/nm.2146"xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://purl.uniprot.org/core/author | "Kawaguchi H."xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://purl.uniprot.org/core/author | "Ikeda T."xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://purl.uniprot.org/core/author | "Nakamura K."xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://purl.uniprot.org/core/author | "Nakagawa T."xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://purl.uniprot.org/core/author | "Saito T."xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://purl.uniprot.org/core/author | "Tokunaga K."xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://purl.uniprot.org/core/author | "Nishida N."xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://purl.uniprot.org/core/author | "Yoshimura N."xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://purl.uniprot.org/core/author | "Mabuchi A."xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://purl.uniprot.org/core/author | "Ohba S."xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://purl.uniprot.org/core/author | "Chung U.I."xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://purl.uniprot.org/core/author | "Akune T."xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://purl.uniprot.org/core/author | "Yano F."xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://purl.uniprot.org/core/author | "Fukai A."xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20495570 | http://purl.uniprot.org/core/name | "Nat Med"xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://purl.uniprot.org/core/pages | "678-686"xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://purl.uniprot.org/core/title | "Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development."xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://purl.uniprot.org/core/volume | "16"xsd:string |
| http://purl.uniprot.org/citations/20495570 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/20495570 |
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| http://purl.uniprot.org/uniprot/#_A0A0G2JG89-mappedCitation-20495570 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20495570 |