The interaction between β1 integrins and ERK1/2 in osteogenic differentiation of human mesenchymal stem cells under fluid shear stress modelled by a perfusion system |
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Authors: | Liyue Liu Chen Zong Bo Li Dan Shen Zihua Tang Jiarong Chen Qiang Zheng Xiangming Tong Changyou Gao Jinfu Wang |
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Institution: | 1. Institute of Cell Biology, College of Life Sciences, Zhejiang University, , Hangzhou, 310058 People's Republic of China;2. Departmant of biology, Ningde Normal University, , Ningde, Fujian, 352101 People's Republic of China;3. Institute of Medical Materials, College of Material and Chemistry, Zhejiang University, , Hangzhou, Zhejiang, 310028 People's Republic of China;4. Laboratory of Bone Marrow, First Hospital, Zhejiang University, , Hangzhou, Zhejiang, 310006 People's Republic of China;5. Institute of Orthopaedics, Second Hospital, Zhejiang University, , Hangzhou, Zhejiang, 310009 People's Republic of China |
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Abstract: | Fluid shear stress (FSS) is an important biomechanical factor regulating the osteogenic differentiation of human mesenchymal stem cells (hMSCs) and is therefore widely used in bone tissue engineering. However, the mechanotransduction of FSS in hMSCs remains largely unknown. As β1 integrins are considered to be important mechanoreceptors in other cells, we suspect that β1 integrins should also be important for hMSCs to sense the stimulation of FSS. We used a perfusion culture system to produce FSS loading on hMSCs seeded in PLGA three‐dimensional (3D) scaffolds and investigated the roles of β1 integrins, FAK and ERK1/2 in FSS‐induced osteogenic differentiation of hMSCs. Our results showed that FSS not only markedly increased ALP activity and the expression of ALP, OCN, Runx2 and COLIα genes but also significantly enhanced the phosphorylation of ERK1/2, Runx2 and FAK. FSS‐induced activation of ERK1/2 and FAK was inhibited by blockade of the connection between β1 integrins and ECM with RGDS peptide and integrins β1 monoclonal antibody. Our study also found that FSS could upregulate the expression level of β1 integrins and that this upregulation could be abolished by PD98059. Further investigation indicated that FSS‐activated ERK1/2 led to the phosphorylation of IκBα and NFκB p65. The activation of NFκB p65 resulted in the upregulation of β1 integrin expression. Therefore, it could be inferred that β1 integrins should sense the stimulation of FSS and thus activate ERK1/2 through activating of FAK, and FSS‐activated ERK1/2 feedback to upregulate the expression of β1 integrins through activating NFκB. Copyright © 2012 John Wiley & Sons, Ltd. |
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Keywords: | fluid shear stress human mesenchymal stem cells β 1 integrins ERK1/2 osteogenic differentiation |
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