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Published in: European Journal of Medical Research 1/2015

Open Access 01-12-2015 | Research

Hypoxia-induced MTA1 promotes MC3T3 osteoblast growth but suppresses MC3T3 osteoblast differentiation

Authors: Tielong Liu, Weiwei Zou, Guodong Shi, Jian Xu, Fei Zhang, Jianru Xiao, Yan Wang

Published in: European Journal of Medical Research | Issue 1/2015

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Abstract

Background

Bone fracture is one of the most common physical injuries in which gene expression and the microenvironment are reprogramed to facilitate the recovery process.

Methods

By specific siRNA transfection and MTT assay, we evaluated the effects of metastasis-associated gene 1 (MTA1) in osteoblast growth. To show the role of MTA1 in osteoblast under hypoxia conditions, by overexpressing and silencing MTA1 expression, we performed mineral deposition and alkaline phosphatase activity assay to observe the differentiation status of osteoblast cells. Real-time PCR and Western blot assays were adopted to detect the expression of certain target genes.

Results

Here, we reported that hypoxia-induced MTA1 expression through hypoxia-induced factor 1 alpha (HIF-1α) and stimulated the growth of osteoblast MC3T3 cells. Silencing of MTA1 through specific siRNA suppressed MC3T3 cell growth and elicited cell differentiation and induced alkaline phosphatase activation and the upregulation of bone morphogenetic protein-2 and osteocalcin.

Conclusions

We found that MTA1 was regulated by HIF-1α in hypoxia circumstance to suppress osteoblast differentiation. These findings provide new insights for bone fracture healing and new strategies to develop potential targets to promote fracture healing.
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Literature
1.
go back to reference Heppenstall RB, Goodwin CW, Brighton CT. Fracture healing in the presence of chronic hypoxia. J Bone Joint Surg Am. 1976;58:1153–6.PubMed Heppenstall RB, Goodwin CW, Brighton CT. Fracture healing in the presence of chronic hypoxia. J Bone Joint Surg Am. 1976;58:1153–6.PubMed
2.
go back to reference Warren SM, Steinbrech DS, Mehrara BJ. Hypoxia regulates osteoblast gene expression. J Surg Res. 2001;99:147–55.CrossRefPubMed Warren SM, Steinbrech DS, Mehrara BJ. Hypoxia regulates osteoblast gene expression. J Surg Res. 2001;99:147–55.CrossRefPubMed
3.
go back to reference Akeno N, Czyzyk-Krzeska MF, Gross TS, Clemens TL. Hypoxia induces vascular endothelial growth factor gene transcription in human osteoblast-like cells through the hypoxia-inducible factor-2alpha. Endocrinology. 2001;142:959–62.PubMed Akeno N, Czyzyk-Krzeska MF, Gross TS, Clemens TL. Hypoxia induces vascular endothelial growth factor gene transcription in human osteoblast-like cells through the hypoxia-inducible factor-2alpha. Endocrinology. 2001;142:959–62.PubMed
4.
go back to reference Bouletreau PJ, Warren SM, Spector JA. Hypoxia and VEGF up-regulate BMP-2 mRNA and protein expression in microvascular endothelial cells: implications for fracture healing. Plast Reconstr Surg. 2002;109:2384–97.CrossRefPubMed Bouletreau PJ, Warren SM, Spector JA. Hypoxia and VEGF up-regulate BMP-2 mRNA and protein expression in microvascular endothelial cells: implications for fracture healing. Plast Reconstr Surg. 2002;109:2384–97.CrossRefPubMed
5.
go back to reference Wang HS, Han JS. Research progress on combat trauma treatment in cold regions. Military Med Res. 2014;1:8.CrossRef Wang HS, Han JS. Research progress on combat trauma treatment in cold regions. Military Med Res. 2014;1:8.CrossRef
6.
go back to reference Hu CJ, Wang LY, Chodosh LA, Keith B, Simon MC. Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation. Mol Cell Biol. 2003;23:9361–74.CrossRefPubMedCentralPubMed Hu CJ, Wang LY, Chodosh LA, Keith B, Simon MC. Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation. Mol Cell Biol. 2003;23:9361–74.CrossRefPubMedCentralPubMed
7.
go back to reference Mazumdar A, Wang RA, Mishra SK. Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor. Nat Cell Biol. 2001;3:30–7.CrossRefPubMed Mazumdar A, Wang RA, Mishra SK. Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor. Nat Cell Biol. 2001;3:30–7.CrossRefPubMed
8.
go back to reference Reddy SD, Pakala SB, Ohshiro K, Rayala SK, Kumar R. MicroRNA-661, a c/EBPalpha target, inhibits metastatic tumor antigen 1 and regulates its functions. Cancer Res. 2009;69:5639–42.CrossRefPubMedCentralPubMed Reddy SD, Pakala SB, Ohshiro K, Rayala SK, Kumar R. MicroRNA-661, a c/EBPalpha target, inhibits metastatic tumor antigen 1 and regulates its functions. Cancer Res. 2009;69:5639–42.CrossRefPubMedCentralPubMed
10.
go back to reference Cui FL, Gong DD, Zhou YJ, Zhu L, Fan Y. Regulatory effect of MTA1 on the anoikis of human prostate cancer cells. Zhonghua Nan Ke Xue. 2011;17:427–30.PubMed Cui FL, Gong DD, Zhou YJ, Zhu L, Fan Y. Regulatory effect of MTA1 on the anoikis of human prostate cancer cells. Zhonghua Nan Ke Xue. 2011;17:427–30.PubMed
11.
go back to reference Yoo YG, Kong G, Lee MO. Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1alpha protein by recruiting histone deacetylase 1. EMBO J. 2006;25(6):1231–41.CrossRefPubMedCentralPubMed Yoo YG, Kong G, Lee MO. Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1alpha protein by recruiting histone deacetylase 1. EMBO J. 2006;25(6):1231–41.CrossRefPubMedCentralPubMed
12.
go back to reference Jin H, Tang LQ, Pan ZG, Peng N, Wen Q, Tang YQ, et al. Ten-year retrospective analysis of multiple trauma complicated by pulmonary contusion. Military Med Res. 2014;1:7.CrossRef Jin H, Tang LQ, Pan ZG, Peng N, Wen Q, Tang YQ, et al. Ten-year retrospective analysis of multiple trauma complicated by pulmonary contusion. Military Med Res. 2014;1:7.CrossRef
13.
go back to reference Gross TS, Akeno N, Clemens TL. Selected contribution: osteocytes upregulate HIF-1alpha in response to acute disuse and oxygen deprivation. J Appl Physiol. 2001;90:2514–9.PubMed Gross TS, Akeno N, Clemens TL. Selected contribution: osteocytes upregulate HIF-1alpha in response to acute disuse and oxygen deprivation. J Appl Physiol. 2001;90:2514–9.PubMed
14.
go back to reference Kim HH, Lee SE, Chung WJ. Stabilization of hypoxia-inducible factor-1alpha is involved in the hypoxic stimuli-induced expression of vascular endothelial growth factor in osteoblastic cells. Cytokine. 2002;17:14–27.CrossRefPubMed Kim HH, Lee SE, Chung WJ. Stabilization of hypoxia-inducible factor-1alpha is involved in the hypoxic stimuli-induced expression of vascular endothelial growth factor in osteoblastic cells. Cytokine. 2002;17:14–27.CrossRefPubMed
15.
go back to reference Sen N, Gui B, Kumar R. Role of MTA1 in cancer progression and metastasis. Cancer Metastasis Rev. 2014;33(4):879–89.CrossRefPubMed Sen N, Gui B, Kumar R. Role of MTA1 in cancer progression and metastasis. Cancer Metastasis Rev. 2014;33(4):879–89.CrossRefPubMed
16.
go back to reference Toh Y, Nicolson GL. The role of the MTA family and their encoded proteins in human cancers: molecular functions and clinical implications. Clin Exp Metastasis. 2009;26:215–27.CrossRefPubMed Toh Y, Nicolson GL. The role of the MTA family and their encoded proteins in human cancers: molecular functions and clinical implications. Clin Exp Metastasis. 2009;26:215–27.CrossRefPubMed
17.
go back to reference Rao Y, Wang H, Fan L, Chen G. Silencing MTA1 by RNAi reverses adhesion, migration and invasiveness of cervical cancer cells (SiHa) via altered expression of p53, and E-cadherin/beta-catenin complex. J Huazhong Univ Sci Technolog Med Sci. 2011;31:1–9.CrossRefPubMed Rao Y, Wang H, Fan L, Chen G. Silencing MTA1 by RNAi reverses adhesion, migration and invasiveness of cervical cancer cells (SiHa) via altered expression of p53, and E-cadherin/beta-catenin complex. J Huazhong Univ Sci Technolog Med Sci. 2011;31:1–9.CrossRefPubMed
18.
go back to reference Hofer MD, Chang MC, Hirko KA, Rubin MA, Nose V. Immunohistochemical and clinicopathological correlation of the metastasis-associated gene 1 (MTA1) expression in benign and malignant pancreatic endocrine tumors. Mod Pathol. 2009;22:933–9.CrossRefPubMed Hofer MD, Chang MC, Hirko KA, Rubin MA, Nose V. Immunohistochemical and clinicopathological correlation of the metastasis-associated gene 1 (MTA1) expression in benign and malignant pancreatic endocrine tumors. Mod Pathol. 2009;22:933–9.CrossRefPubMed
19.
go back to reference Manavathi B, Singh K, Kumar R. MTA family of coregulators in nuclear receptor biology and pathology. Nucl Recept Signal. 2007;5:e010.PubMedCentralPubMed Manavathi B, Singh K, Kumar R. MTA family of coregulators in nuclear receptor biology and pathology. Nucl Recept Signal. 2007;5:e010.PubMedCentralPubMed
20.
go back to reference Xu L, Mao XY, Fan CF, Zheng HC. MTA1 expression correlates significantly with cigarette smoke in non-small cell lung cancer. Virchows Arch. 2011;459:415–22.CrossRefPubMed Xu L, Mao XY, Fan CF, Zheng HC. MTA1 expression correlates significantly with cigarette smoke in non-small cell lung cancer. Virchows Arch. 2011;459:415–22.CrossRefPubMed
21.
go back to reference Jarrett RB, Schaffer M, McIntire D, Witt-Browder A, Kraft D, Risser RC. Treatment of atypical depression with cognitive therapy or phenelzine: a double-blind, placebo-controlled trial. Arch Gen Psychiatry. 1999;56:431–7.CrossRefPubMedCentralPubMed Jarrett RB, Schaffer M, McIntire D, Witt-Browder A, Kraft D, Risser RC. Treatment of atypical depression with cognitive therapy or phenelzine: a double-blind, placebo-controlled trial. Arch Gen Psychiatry. 1999;56:431–7.CrossRefPubMedCentralPubMed
22.
go back to reference Lechler P, Klein SM, Prantl L, Englert C, Renkawitz T, Grifka J. Hypoxic downregulation of cellular proliferation and loss of phenotype stability in human osteoblasts is mediated by HIF-1alpha. Clin Hemorheol Microcirc. 2011;49:279–86.PubMed Lechler P, Klein SM, Prantl L, Englert C, Renkawitz T, Grifka J. Hypoxic downregulation of cellular proliferation and loss of phenotype stability in human osteoblasts is mediated by HIF-1alpha. Clin Hemorheol Microcirc. 2011;49:279–86.PubMed
23.
go back to reference Tamama K, Kawasaki H, Kerpedjieva SS, Guan J, Ganju RK, Sen CK. Differential roles of hypoxia inducible factor subunits in multipotential stromal cells under hypoxic condition. J Cell Biochem. 2011;112:804–17.CrossRefPubMedCentralPubMed Tamama K, Kawasaki H, Kerpedjieva SS, Guan J, Ganju RK, Sen CK. Differential roles of hypoxia inducible factor subunits in multipotential stromal cells under hypoxic condition. J Cell Biochem. 2011;112:804–17.CrossRefPubMedCentralPubMed
Metadata
Title
Hypoxia-induced MTA1 promotes MC3T3 osteoblast growth but suppresses MC3T3 osteoblast differentiation
Authors
Tielong Liu
Weiwei Zou
Guodong Shi
Jian Xu
Fei Zhang
Jianru Xiao
Yan Wang
Publication date
01-12-2015
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2015
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-015-0084-x

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