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    Please use this identifier to cite or link to this item: https://tkuir.lib.tku.edu.tw/dspace/handle/987654321/76988


    Title: Hypoxia Inhibits Osteogenesis in Human Mesenchymal Stem Cells through Direct Regulation of RUNX2 by TWIST
    Authors: Yang, Der-Chih;Yang, Muh-Hwa;Tsai, Chih-Chien;Huang, Tung-Fu;Chen, Yau-Hung;Hung, Shih-Chieh
    Contributors: 淡江大學化學學系
    Date: 2011-09-01
    Issue Date: 2012-05-23 15:25:30 (UTC+8)
    Publisher: San Francisco: Public Library of Science
    Abstract: Background: Bone loss induced by hypoxia is associated with various pathophysiological conditions, however, little is known about the effects of hypoxia and related signaling pathways on osteoblast differentiation and bone formation. Because bone marrow-derived mesenchymal stem cells (MSCs) survive under hypoxic conditions and readily differentiate into osteoblasts by standard induction protocols, they are a good in vitro model to study the effects of hypoxia on osteoblast differentiation.
    Methodology/Principle Findings: Using human MSCs, we discovered TWIST, a downstream target of HIF-1α;, was induced under hypoxia and acted as a transcription repressor of RUNX2 through binding to the E-box located on the promoter of type 1 RUNX2. Suppression of type 1 RUNX2 by TWIST under hypoxia further inhibited the expression of BMP2, type 2 RUNX2 and downstream targets of RUNX2 in MSCs.
    Conclusions/Significance: Our findings point to the important role of hypoxia-mediated signalling in osteogenic differentiation in MSCs through direct regulation of RUNX2 by TWIST, and provide a method for modifying MSC osteogenesis upon application of these cells in fracture healing and bone reconstruction.
    Relation: PLoS ONE 6(9), e2365(10pages)
    DOI: 10.1371/journal.pone.0023965
    Appears in Collections:[化學學系暨研究所] 期刊論文

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