The transcription factor snail regulates osteogenic differentiation by repressing Runx2 expression

Su Jin Park; Seung Hyun Jung; Gadi Jogeswar; Hyun Mo Ryoo; Jong In Yook; Han Seok Choi; Yumie Rhee; Cheol Hee Kim; Sung Kil Lim

doi:10.1016/j.bone.2010.02.027

The transcription factor snail regulates osteogenic differentiation by repressing Runx2 expression

Su Jin Park, Seung Hyun Jung, Gadi Jogeswar, Hyun Mo Ryoo, Jong In Yook, Han Seok Choi, Yumie Rhee, Cheol Hee Kim, Sung Kil Lim

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1498-1507
Number of pages	10
Journal	Bone
Volume	46
Issue number	6
DOIs	https://doi.org/10.1016/j.bone.2010.02.027
Publication status	Published - 2010 Jun

Bibliographical note

Funding 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
Physiology
Histology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bone.2010.02.027

Cite this

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title = "The transcription factor snail regulates osteogenic differentiation by repressing Runx2 expression",

abstract = "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.",

author = "Park, {Su Jin} and Jung, {Seung Hyun} and Gadi Jogeswar and Ryoo, {Hyun Mo} and Yook, {Jong In} and Choi, {Han Seok} and Yumie Rhee and Kim, {Cheol Hee} and Lim, {Sung Kil}",

note = "Funding 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.",

year = "2010",

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doi = "10.1016/j.bone.2010.02.027",

language = "English",

volume = "46",

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AU - Yook, Jong In

AU - Choi, Han Seok

AU - Rhee, Yumie

AU - Kim, Cheol Hee

AU - Lim, Sung Kil

N1 - Funding 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.

PY - 2010/6

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N2 - 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.

AB - 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.

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The transcription factor snail regulates osteogenic differentiation by repressing Runx2 expression

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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