Physical and functional interactions between Runx2 and HIF‐1α induce vascular endothelial growth factor gene expression
dc.contributor.author | Kwon, Tae‐geon | en_US |
dc.contributor.author | Zhao, Xiang | en_US |
dc.contributor.author | Yang, Qian | en_US |
dc.contributor.author | Li, Yan | en_US |
dc.contributor.author | Ge, Chunxi | en_US |
dc.contributor.author | Zhao, Guisheng | en_US |
dc.contributor.author | Franceschi, Renny T. | en_US |
dc.date.accessioned | 2011-11-10T15:35:00Z | |
dc.date.available | 2013-02-01T20:26:15Z | en_US |
dc.date.issued | 2011-12 | en_US |
dc.identifier.citation | Kwon, Tae‐geon ; Zhao, Xiang; Yang, Qian; Li, Yan; Ge, Chunxi; Zhao, Guisheng; Franceschi, Renny T. (2011). "Physical and functional interactions between Runx2 and HIFâ 1α induce vascular endothelial growth factor gene expression ." Journal of Cellular Biochemistry 112(12): 3582-3593. <http://hdl.handle.net/2027.42/86966> | en_US |
dc.identifier.issn | 0730-2312 | en_US |
dc.identifier.issn | 1097-4644 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/86966 | |
dc.description.abstract | Angiogenesis and bone formation are intimately related processes. Hypoxia during early bone development stabilizes hypoxia‐inducible factor‐1α (HIF‐1α) and increases angiogenic signals including vascular endothelial growth factor (VEGF). Furthermore, stabilization of HIF‐1α by genetic or chemical means stimulates bone formation. On the other hand, deficiency of Runx2, a key osteogenic transcription factor, prevents vascular invasion of bone and VEGF expression. This study explores the possibility that HIF‐1α and Runx2 interact to activate angiogenic signals. Runx2 over‐expression in mesenchymal cells increased VEGF mRNA and protein under both normoxic and hypoxic conditions. In normoxia, Runx2 also dramatically increased HIF‐1α protein. In all cases, the Runx2 response was inhibited by siRNA‐mediated suppression of HIF‐1α and completely blocked by the HIF‐1α inhibitor, echinomycin. Similarly, treatment of preosteoblast cells with Runx2 siRNA reduced VEGF mRNA in normoxia or hypoxia. However, Runx2 is not essential for the HIF‐1α response since VEGF is induced by hypoxia even in Runx2‐null cells. Endogenous Runx2 and HIF‐1α were colocalized to the nuclei of MC3T3‐E1 preosteoblast cells. Moreover, HIF‐1α and Runx2 physically interact using sites within the Runx2 RUNT domain. Chromatin immunoprecipitation also provided evidence for colocalization of Runx2 and HIF‐1α on the VEGF promoter. In addition, Runx2 stimulated HIF‐1α‐dependent activation of an HRE‐luciferase reporter gene without requiring a separate Runx2‐binding enhancer. These studies indicate that Runx2 functions together with HIF‐1α to stimulate angiogenic gene expression in bone cells and may in part explain the known requirement for Runx2 in bone vascularization. J. Cell. Biochem. 112: 3582–3593, 2011. © 2011 Wiley Periodicals, Inc. | en_US |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Osteoblast | en_US |
dc.subject.other | Vascularization | en_US |
dc.subject.other | Angiogenesis | en_US |
dc.subject.other | Transcriptional Factors | en_US |
dc.subject.other | Hypoxia | en_US |
dc.title | Physical and functional interactions between Runx2 and HIF‐1α induce vascular endothelial growth factor gene expression | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Genetics | en_US |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Periodontics & Oral Medicine and Biological Chemistry, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, 1011 N. University Ave, Ann Arbor, MI 48109‐1078, USA. | en_US |
dc.contributor.affiliationother | Department of Oral & Maxillofacial Surgery, Kyungpook National University, Daegu, Republic of Korea | en_US |
dc.identifier.pmid | 21793044 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/86966/1/23289_ftp.pdf | |
dc.identifier.doi | 10.1002/jcb.23289 | en_US |
dc.identifier.source | Journal of Cellular Biochemistry | en_US |
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dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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