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.
Bibliographical noteFunding Information:
We are grateful to Choi Won-Iil (Yonsei University, Seoul, Korea) for the technical support. This work was supported by the Science Research Center grant to Bone Metabolism Research Center ( 2009-0063265 ) funded by the Korean Ministry of Education, Science and Technology. This work was also supported by the Brain Korea 21 Project for Medical Science, Yonsei University . Kim CH was supported by grant FG09-42-1 of the 21C Frontier Functional Human Genome Project from the Ministry of Science & Technology in Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism