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Title: NRF2 overexpression in mesenchymal stem cells induces stem-cell marker expression and enhances osteoblastic differentiation

Abstract

Hypoxic environment has been suggested in stem cell culturing as their physiologic niche requires oxygen tension to maintain stemness. The administration of cobalt chloride (CoCl{sub 2}) was widely applied in mimicking hypoxia for its economic advantages and convenience. We confirmed that CoCl{sub 2} could maintain stemness and promote the osteogenesis capacity of MSCs. However, CoCl{sub 2} could induce the apoptosis and hinder the proliferation of MSCs. To find out a potential method maintaining their stemness without threatening their survival, we analyzed the database of Gene Expression Omnibus (GEO) and proposed that NRF2 (nuclear factor erythroid-derived 2-like 2) might be the potential target. We found that knocking down NRF2 expression in MSCs impaired the expression of stem cell markers and the osteogenesis process even under hypoxic environment, but with NRF2 overexpression, the proliferation of MSCs was increased with significantly reduced rate of apoptosis. Therefore, our findings suggested that overexpressing NRF2 could be a potential method for maintaining stemness and preventing apoptosis in MSCs under oxidative stress. - Highlights: • Hypoxia promoted Stemness maintenance and osteogenesis. • NRF2 maybe the bridge that connects stemness and apoptosis under oxidative stress. • NRF2 deficiency impaired the effect of hypoxia on stemness and osteogenesis. •more » NRF2 promoted the maintenance of stem cell characteristics and prevented apoptosis.« less

Authors:
;  [1];  [2];  [3];  [1];  [4];  [5];  [6];  [1];  [2];  [4];  [1];  [5];  [2]
  1. Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630 (China)
  2. (China)
  3. Department of Thyroid and Breast Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630 (China)
  4. Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630 (China)
  5. Organ Transplantation Institute of Sun Yat-sen University, Guangzhou 510630 (China)
  6. Cell-Gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital of SunYat-Sen University, Guangzhou 510630 (China)
Publication Date:
OSTI Identifier:
22719074
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 491; Journal Issue: 1; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANOXIA; APOPTOSIS; CELL CULTURES; CELL PROLIFERATION; OXIDATION; OXYGEN; STEM CELLS

Citation Formats

Yuan, Zenan, Zhang, Jian, Organ Transplantation Institute of Sun Yat-sen University, Guangzhou 510630, Huang, Yong, Zhang, Yingcai, Liu, Wei, Wang, Genshu, Zhang, Qi, Wang, Guoying, Organ Transplantation Institute of Sun Yat-sen University, Guangzhou 510630, Yang, Yang, Li, Hua, Chen, Guihua, and Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630. NRF2 overexpression in mesenchymal stem cells induces stem-cell marker expression and enhances osteoblastic differentiation. United States: N. p., 2017. Web. doi:10.1016/J.BBRC.2017.07.083.
Yuan, Zenan, Zhang, Jian, Organ Transplantation Institute of Sun Yat-sen University, Guangzhou 510630, Huang, Yong, Zhang, Yingcai, Liu, Wei, Wang, Genshu, Zhang, Qi, Wang, Guoying, Organ Transplantation Institute of Sun Yat-sen University, Guangzhou 510630, Yang, Yang, Li, Hua, Chen, Guihua, & Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630. NRF2 overexpression in mesenchymal stem cells induces stem-cell marker expression and enhances osteoblastic differentiation. United States. doi:10.1016/J.BBRC.2017.07.083.
Yuan, Zenan, Zhang, Jian, Organ Transplantation Institute of Sun Yat-sen University, Guangzhou 510630, Huang, Yong, Zhang, Yingcai, Liu, Wei, Wang, Genshu, Zhang, Qi, Wang, Guoying, Organ Transplantation Institute of Sun Yat-sen University, Guangzhou 510630, Yang, Yang, Li, Hua, Chen, Guihua, and Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630. Sat . "NRF2 overexpression in mesenchymal stem cells induces stem-cell marker expression and enhances osteoblastic differentiation". United States. doi:10.1016/J.BBRC.2017.07.083.
@article{osti_22719074,
title = {NRF2 overexpression in mesenchymal stem cells induces stem-cell marker expression and enhances osteoblastic differentiation},
author = {Yuan, Zenan and Zhang, Jian and Organ Transplantation Institute of Sun Yat-sen University, Guangzhou 510630 and Huang, Yong and Zhang, Yingcai and Liu, Wei and Wang, Genshu and Zhang, Qi and Wang, Guoying and Organ Transplantation Institute of Sun Yat-sen University, Guangzhou 510630 and Yang, Yang and Li, Hua and Chen, Guihua and Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630},
abstractNote = {Hypoxic environment has been suggested in stem cell culturing as their physiologic niche requires oxygen tension to maintain stemness. The administration of cobalt chloride (CoCl{sub 2}) was widely applied in mimicking hypoxia for its economic advantages and convenience. We confirmed that CoCl{sub 2} could maintain stemness and promote the osteogenesis capacity of MSCs. However, CoCl{sub 2} could induce the apoptosis and hinder the proliferation of MSCs. To find out a potential method maintaining their stemness without threatening their survival, we analyzed the database of Gene Expression Omnibus (GEO) and proposed that NRF2 (nuclear factor erythroid-derived 2-like 2) might be the potential target. We found that knocking down NRF2 expression in MSCs impaired the expression of stem cell markers and the osteogenesis process even under hypoxic environment, but with NRF2 overexpression, the proliferation of MSCs was increased with significantly reduced rate of apoptosis. Therefore, our findings suggested that overexpressing NRF2 could be a potential method for maintaining stemness and preventing apoptosis in MSCs under oxidative stress. - Highlights: • Hypoxia promoted Stemness maintenance and osteogenesis. • NRF2 maybe the bridge that connects stemness and apoptosis under oxidative stress. • NRF2 deficiency impaired the effect of hypoxia on stemness and osteogenesis. • NRF2 promoted the maintenance of stem cell characteristics and prevented apoptosis.},
doi = {10.1016/J.BBRC.2017.07.083},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 491,
place = {United States},
year = {2017},
month = {9}
}