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Glucocorticoid Receptor and Sequential P53 Activation by Dexamethasone Mediates Apoptosis and Cell Cycle Arrest of Osteoblastic MC3T3-E1 Cells

Glucocorticoids play a pivotal role in the proliferation of osteoblasts, but the underlying mechanism has not been successfully elucidated. In this report, we have investigated the molecular mechanism which elucidates the inhibitory effects of dexamethasone on murine osteoblastic MC3T3-E1 cells. It...

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Autores principales: Li, Hui, Qian, Wenwei, Weng, Xisheng, Wu, Zhihong, Li, Huihua, Zhuang, Qianyu, Feng, Bin, Bian, Yanyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375272/
https://www.ncbi.nlm.nih.gov/pubmed/22719835
http://dx.doi.org/10.1371/journal.pone.0037030
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author Li, Hui
Qian, Wenwei
Weng, Xisheng
Wu, Zhihong
Li, Huihua
Zhuang, Qianyu
Feng, Bin
Bian, Yanyan
author_facet Li, Hui
Qian, Wenwei
Weng, Xisheng
Wu, Zhihong
Li, Huihua
Zhuang, Qianyu
Feng, Bin
Bian, Yanyan
author_sort Li, Hui
collection PubMed
description Glucocorticoids play a pivotal role in the proliferation of osteoblasts, but the underlying mechanism has not been successfully elucidated. In this report, we have investigated the molecular mechanism which elucidates the inhibitory effects of dexamethasone on murine osteoblastic MC3T3-E1 cells. It was found that the inhibitory effects were largely attributed to apoptosis and G1 phase arrest. Both the cell cycle arrest and apoptosis were dependent on glucocorticoid receptor (GR), as they were abolished by GR blocker RU486 pre-treatment and GR interference. G1 phase arrest and apoptosis were accompanied with a p53-dependent up-regulation of p21 and pro-apoptotic genes NOXA and PUMA. We also proved that dexamethasone can’t induce apoptosis and cell cycle arrest when p53 was inhibited by p53 RNA interference. These data demonstrate that proliferation of MC3T3-E1 cell was significantly and directly inhibited by dexamethasone treatment via aberrant GR activation and subsequently P53 activation.
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spelling pubmed-33752722012-06-20 Glucocorticoid Receptor and Sequential P53 Activation by Dexamethasone Mediates Apoptosis and Cell Cycle Arrest of Osteoblastic MC3T3-E1 Cells Li, Hui Qian, Wenwei Weng, Xisheng Wu, Zhihong Li, Huihua Zhuang, Qianyu Feng, Bin Bian, Yanyan PLoS One Research Article Glucocorticoids play a pivotal role in the proliferation of osteoblasts, but the underlying mechanism has not been successfully elucidated. In this report, we have investigated the molecular mechanism which elucidates the inhibitory effects of dexamethasone on murine osteoblastic MC3T3-E1 cells. It was found that the inhibitory effects were largely attributed to apoptosis and G1 phase arrest. Both the cell cycle arrest and apoptosis were dependent on glucocorticoid receptor (GR), as they were abolished by GR blocker RU486 pre-treatment and GR interference. G1 phase arrest and apoptosis were accompanied with a p53-dependent up-regulation of p21 and pro-apoptotic genes NOXA and PUMA. We also proved that dexamethasone can’t induce apoptosis and cell cycle arrest when p53 was inhibited by p53 RNA interference. These data demonstrate that proliferation of MC3T3-E1 cell was significantly and directly inhibited by dexamethasone treatment via aberrant GR activation and subsequently P53 activation. Public Library of Science 2012-06-14 /pmc/articles/PMC3375272/ /pubmed/22719835 http://dx.doi.org/10.1371/journal.pone.0037030 Text en Li et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Li, Hui
Qian, Wenwei
Weng, Xisheng
Wu, Zhihong
Li, Huihua
Zhuang, Qianyu
Feng, Bin
Bian, Yanyan
Glucocorticoid Receptor and Sequential P53 Activation by Dexamethasone Mediates Apoptosis and Cell Cycle Arrest of Osteoblastic MC3T3-E1 Cells
title Glucocorticoid Receptor and Sequential P53 Activation by Dexamethasone Mediates Apoptosis and Cell Cycle Arrest of Osteoblastic MC3T3-E1 Cells
title_full Glucocorticoid Receptor and Sequential P53 Activation by Dexamethasone Mediates Apoptosis and Cell Cycle Arrest of Osteoblastic MC3T3-E1 Cells
title_fullStr Glucocorticoid Receptor and Sequential P53 Activation by Dexamethasone Mediates Apoptosis and Cell Cycle Arrest of Osteoblastic MC3T3-E1 Cells
title_full_unstemmed Glucocorticoid Receptor and Sequential P53 Activation by Dexamethasone Mediates Apoptosis and Cell Cycle Arrest of Osteoblastic MC3T3-E1 Cells
title_short Glucocorticoid Receptor and Sequential P53 Activation by Dexamethasone Mediates Apoptosis and Cell Cycle Arrest of Osteoblastic MC3T3-E1 Cells
title_sort glucocorticoid receptor and sequential p53 activation by dexamethasone mediates apoptosis and cell cycle arrest of osteoblastic mc3t3-e1 cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375272/
https://www.ncbi.nlm.nih.gov/pubmed/22719835
http://dx.doi.org/10.1371/journal.pone.0037030
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