Ox-LDL modifies the behaviour of bone marrow stem cells and impairs their endothelial differentiation via inhibition of Akt phosphorylation

This study was to investigate the effect of oxidized low-density lipoprotein (ox-LDL) on the behaviour of bone marrow stem cells and their endothelial differentiation as well as the underlying mechanisms. Adult rat bone marrow multipotent progenitor cells (MAPCs) were incubated with ox-LDL for up to...

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Main Authors:	Chu, Ling, Hao, Hong, Luo, Min, Huang, Yu, Chen, Zhenyu, Lu, Tiewei, Zhao, Xue, Verfaillie, Catherine M, Zweier, Jay L, Liu, Zhenguo
Format:	Online
Language:	English
Published:	Blackwell Publishing Ltd 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822806/

id	pubmed-3822806
recordtype	oai_dc
spelling	pubmed-38228062015-04-06 Ox-LDL modifies the behaviour of bone marrow stem cells and impairs their endothelial differentiation via inhibition of Akt phosphorylation Chu, Ling Hao, Hong Luo, Min Huang, Yu Chen, Zhenyu Lu, Tiewei Zhao, Xue Verfaillie, Catherine M Zweier, Jay L Liu, Zhenguo Articles This study was to investigate the effect of oxidized low-density lipoprotein (ox-LDL) on the behaviour of bone marrow stem cells and their endothelial differentiation as well as the underlying mechanisms. Adult rat bone marrow multipotent progenitor cells (MAPCs) were incubated with ox-LDL for up to 2 weeks. Ox-LDL treatment resulted in a time- and dose-dependent reduction of MAPC population in culture through a combination of decreased cell proliferation and increased apoptosis. The expression of stem cell marker Oct-4 was significantly suppressed in MAPCs by ox-LDL in a dose- and time-dependant manner. Endothelial differentiation of MAPCs was substantially inhibited by ox-LDL with markedly decreased expression of endothelial markers vWF, Flk-1 and CD31, as well as impaired in vitro vascular structure formation. Ox-LDL-induced apoptosis and inhibition of Oct-4 expression, cell proliferation and endothelial differentiation of MAPCs were associated with significant inhibition of Akt phosphorylation. Akt overexpression in MAPCs transfected with a constitutively active Akt completely reversed the effects of ox-LDL on MAPCs including enhanced apoptosis, decreased cell proliferation, suppressed Oct-4 expression and endothelial differentiation as well as in vitro vascular structure formation. In conclusion, ox-LDL promotes apoptosis and inhibits Oct-4 expression and self-renewal of MAPCs, and impairs their endothelial differentiation via suppression of Akt signalling. Blackwell Publishing Ltd 2011-02 2009-10-23 /pmc/articles/PMC3822806/ /pubmed/19863696 http://dx.doi.org/10.1111/j.1582-4934.2009.00948.x Text en © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Chu, Ling Hao, Hong Luo, Min Huang, Yu Chen, Zhenyu Lu, Tiewei Zhao, Xue Verfaillie, Catherine M Zweier, Jay L Liu, Zhenguo
spellingShingle	Chu, Ling Hao, Hong Luo, Min Huang, Yu Chen, Zhenyu Lu, Tiewei Zhao, Xue Verfaillie, Catherine M Zweier, Jay L Liu, Zhenguo Ox-LDL modifies the behaviour of bone marrow stem cells and impairs their endothelial differentiation via inhibition of Akt phosphorylation
author_facet	Chu, Ling Hao, Hong Luo, Min Huang, Yu Chen, Zhenyu Lu, Tiewei Zhao, Xue Verfaillie, Catherine M Zweier, Jay L Liu, Zhenguo
author_sort	Chu, Ling
title	Ox-LDL modifies the behaviour of bone marrow stem cells and impairs their endothelial differentiation via inhibition of Akt phosphorylation
title_short	Ox-LDL modifies the behaviour of bone marrow stem cells and impairs their endothelial differentiation via inhibition of Akt phosphorylation
title_full	Ox-LDL modifies the behaviour of bone marrow stem cells and impairs their endothelial differentiation via inhibition of Akt phosphorylation
title_fullStr	Ox-LDL modifies the behaviour of bone marrow stem cells and impairs their endothelial differentiation via inhibition of Akt phosphorylation
title_full_unstemmed	Ox-LDL modifies the behaviour of bone marrow stem cells and impairs their endothelial differentiation via inhibition of Akt phosphorylation
title_sort	ox-ldl modifies the behaviour of bone marrow stem cells and impairs their endothelial differentiation via inhibition of akt phosphorylation
description	This study was to investigate the effect of oxidized low-density lipoprotein (ox-LDL) on the behaviour of bone marrow stem cells and their endothelial differentiation as well as the underlying mechanisms. Adult rat bone marrow multipotent progenitor cells (MAPCs) were incubated with ox-LDL for up to 2 weeks. Ox-LDL treatment resulted in a time- and dose-dependent reduction of MAPC population in culture through a combination of decreased cell proliferation and increased apoptosis. The expression of stem cell marker Oct-4 was significantly suppressed in MAPCs by ox-LDL in a dose- and time-dependant manner. Endothelial differentiation of MAPCs was substantially inhibited by ox-LDL with markedly decreased expression of endothelial markers vWF, Flk-1 and CD31, as well as impaired in vitro vascular structure formation. Ox-LDL-induced apoptosis and inhibition of Oct-4 expression, cell proliferation and endothelial differentiation of MAPCs were associated with significant inhibition of Akt phosphorylation. Akt overexpression in MAPCs transfected with a constitutively active Akt completely reversed the effects of ox-LDL on MAPCs including enhanced apoptosis, decreased cell proliferation, suppressed Oct-4 expression and endothelial differentiation as well as in vitro vascular structure formation. In conclusion, ox-LDL promotes apoptosis and inhibits Oct-4 expression and self-renewal of MAPCs, and impairs their endothelial differentiation via suppression of Akt signalling.
publisher	Blackwell Publishing Ltd
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822806/
_version_	1612025104756113408

Ox-LDL modifies the behaviour of bone marrow stem cells and impairs their endothelial differentiation via inhibition of Akt phosphorylation

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