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SLUG: a new target of lymphoid enhancer factor-1 in human osteoblasts
BACKGROUND: Lymphoid Enhancer Factor-1 (Lef-1) is a member of a transcription factor family that acts as downstream mediator of the Wnt/β-catenin signalling pathway which plays a critical role in osteoblast proliferation and differentiation. In a search for Lef-1 responsive genes in human osteoblast...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834684/ https://www.ncbi.nlm.nih.gov/pubmed/20128911 http://dx.doi.org/10.1186/1471-2199-11-13 |
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author | Lambertini, Elisabetta Franceschetti, Tiziana Torreggiani, Elena Penolazzi, Letizia Pastore, Antonio Pelucchi, Stefano Gambari, Roberto Piva, Roberta |
author_facet | Lambertini, Elisabetta Franceschetti, Tiziana Torreggiani, Elena Penolazzi, Letizia Pastore, Antonio Pelucchi, Stefano Gambari, Roberto Piva, Roberta |
author_sort | Lambertini, Elisabetta |
collection | PubMed |
description | BACKGROUND: Lymphoid Enhancer Factor-1 (Lef-1) is a member of a transcription factor family that acts as downstream mediator of the Wnt/β-catenin signalling pathway which plays a critical role in osteoblast proliferation and differentiation. In a search for Lef-1 responsive genes in human osteoblasts, we focused on the transcriptional regulation of the SLUG, a zinc finger transcription factor belonging to the Snail family of developmental proteins. Although the role of SLUG in epithelial-mesenchymal transition and cell motility during embryogenesis is well documented, the functions of this factor in most normal adult human tissues are largely unknown. In this study we investigated SLUG expression in normal human osteoblasts and their mesenchymal precursors, and its possible correlation with Lef-1 and Wnt/β-catenin signalling. RESULTS: The experiments were performed on normal human primary osteoblasts obtained from bone fragments, cultured in osteogenic conditions in presence of Lef-1 expression vector or GSK-3β inhibitor, SB216763. We demonstrated that the transcription factor SLUG is present in osteoblasts as well as in their mesenchymal precursors obtained from Wharton's Jelly of human umbilical cord and induced to osteoblastic differentiation. We found that SLUG is positively correlated with RUNX2 expression and deposition of mineralized matrix, and is regulated by Lef-1 and β-catenin. Consistently, Chromatin Immunoprecipitation (ChIP) assay, used to detect the direct Lef/Tcf factors that are responsible for the promoter activity of SLUG gene, demonstrated that Lef-1, TCF-1 and TCF4 are recruited to the SLUG gene promoter "in vivo". CONCLUSION: These studies provide, for the first time, the evidence that SLUG expression is correlated with osteogenic commitment, and is positively regulated by Lef-1 signal in normal human osteoblasts. These findings will help to further understand the regulation of the human SLUG gene and reveal the biological functions of SLUG in the context of bone tissue. |
format | Text |
id | pubmed-2834684 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-28346842010-03-09 SLUG: a new target of lymphoid enhancer factor-1 in human osteoblasts Lambertini, Elisabetta Franceschetti, Tiziana Torreggiani, Elena Penolazzi, Letizia Pastore, Antonio Pelucchi, Stefano Gambari, Roberto Piva, Roberta BMC Mol Biol Research article BACKGROUND: Lymphoid Enhancer Factor-1 (Lef-1) is a member of a transcription factor family that acts as downstream mediator of the Wnt/β-catenin signalling pathway which plays a critical role in osteoblast proliferation and differentiation. In a search for Lef-1 responsive genes in human osteoblasts, we focused on the transcriptional regulation of the SLUG, a zinc finger transcription factor belonging to the Snail family of developmental proteins. Although the role of SLUG in epithelial-mesenchymal transition and cell motility during embryogenesis is well documented, the functions of this factor in most normal adult human tissues are largely unknown. In this study we investigated SLUG expression in normal human osteoblasts and their mesenchymal precursors, and its possible correlation with Lef-1 and Wnt/β-catenin signalling. RESULTS: The experiments were performed on normal human primary osteoblasts obtained from bone fragments, cultured in osteogenic conditions in presence of Lef-1 expression vector or GSK-3β inhibitor, SB216763. We demonstrated that the transcription factor SLUG is present in osteoblasts as well as in their mesenchymal precursors obtained from Wharton's Jelly of human umbilical cord and induced to osteoblastic differentiation. We found that SLUG is positively correlated with RUNX2 expression and deposition of mineralized matrix, and is regulated by Lef-1 and β-catenin. Consistently, Chromatin Immunoprecipitation (ChIP) assay, used to detect the direct Lef/Tcf factors that are responsible for the promoter activity of SLUG gene, demonstrated that Lef-1, TCF-1 and TCF4 are recruited to the SLUG gene promoter "in vivo". CONCLUSION: These studies provide, for the first time, the evidence that SLUG expression is correlated with osteogenic commitment, and is positively regulated by Lef-1 signal in normal human osteoblasts. These findings will help to further understand the regulation of the human SLUG gene and reveal the biological functions of SLUG in the context of bone tissue. BioMed Central 2010-02-03 /pmc/articles/PMC2834684/ /pubmed/20128911 http://dx.doi.org/10.1186/1471-2199-11-13 Text en Copyright ©2010 Lambertini et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research article Lambertini, Elisabetta Franceschetti, Tiziana Torreggiani, Elena Penolazzi, Letizia Pastore, Antonio Pelucchi, Stefano Gambari, Roberto Piva, Roberta SLUG: a new target of lymphoid enhancer factor-1 in human osteoblasts |
title | SLUG: a new target of lymphoid enhancer factor-1 in human osteoblasts |
title_full | SLUG: a new target of lymphoid enhancer factor-1 in human osteoblasts |
title_fullStr | SLUG: a new target of lymphoid enhancer factor-1 in human osteoblasts |
title_full_unstemmed | SLUG: a new target of lymphoid enhancer factor-1 in human osteoblasts |
title_short | SLUG: a new target of lymphoid enhancer factor-1 in human osteoblasts |
title_sort | slug: a new target of lymphoid enhancer factor-1 in human osteoblasts |
topic | Research article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834684/ https://www.ncbi.nlm.nih.gov/pubmed/20128911 http://dx.doi.org/10.1186/1471-2199-11-13 |
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