Journal
BONE
Volume 46, Issue 6, Pages 1498-1507Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2010.02.027
Keywords
Snail; Runx2; E-box; Osteogenic differentiation
Categories
Funding
- Korean Ministry of Education, Science and Technology [2009-0063265]
- Brain Korea 21 Project for Medical Science, Yonsei University
- Ministry of Science & Technology in Korea [FG09-42-1]
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Osteoblasts originate from mesenchymal stem cells by the coordinated activities of different signaling pathways that regulate the expression of osteoblast-specific genes. Runt-related transcription factor 2 (Runx2) is the master transcription factor for osteoblast differentiation. Despite the importance of Runx2 in the developing skeleton, how Runx2 expression is regulated remains a pivotal question. Snail, a zinc finger transcription factor, is essential for triggering epithelial-to-mesenchymal transitions (EMTs) during embryonic development and tumor progression. Here, we report that Runx2 expression is significantly up- or down-regulated relative to Snail expression. We demonstrate that Snail binds to the Runx2 promoter and that repression of Runx2 transcription by Snail is dependent on specific E-box sequence within the promoter. With antisense morpholino oligonucleotide (MO)-mediated knockdown of Snail expression in zebrafish, we observed alterations in osteogenic potential. These results indicate that Snail plays a crucial role in osteogenic differentiation by acting as a direct Runx2 repressor. (C) 2010 Elsevier Inc. All rights reserved.
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