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Osteopontin Promotes Mesenchymal Stem Cell Migration and Lessens Cell Stiffness via Integrin β1, FAK, and ERK Pathways

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Abstract

The use of mesenchymal stem cells (MSCs) for therapeutic applications has attracted great attention because MSCs home to and engraft to injured tissues after in vivo administration. The expression of osteopontin (OPN) is elevated in response to injury and inflammation, and its role on rat bone marrow-derived mesenchymal stem cells (rMSCs)-directed migration has been elucidated. However, the signaling pathways through the activation of which OPN promotes rMSCs migration and the involvement of cell mechanics during OPN-mediating rMSCs migration have not been well studied. In this study, we found that OPN activated focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK) signaling pathways by the ligation of integrin β1 in rMSCs. Inhibitors of FAK and ERK pathways inhibited OPN-induced rMSCs migration, indicating the possible involvement of FAK and ERK activation in OPN-induced migration in rMSCs. In addition, atomic force microscopy analysis showed that OPN reduced cell stiffness in rMSCs via integrin β1, FAK, and ERK pathways, suggesting that the promotion of rMSCs migration might partially be contributing to the decrease in cell stiffness stimulated by OPN. To further examine the role of OPN on cell motility and stiffness, actin cytoskeleton of rMSCs was observed. The reduced well-defined F-actin filaments and the promoted formation of pseudopodia in rMSCs induced by OPN explained the reduction in cell stiffness and the increase in cell migration. The current study data have shown for the first time that OPN binding to integrin β1 promotes rMSCs migration through the activation of FAK and ERK pathways, which may be attributed to the change in cell stiffness caused by the reduction in the amount of organized actin cytoskeleton.

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Acknowledgments

This study was supported by grants from the Natural National Science Foundation of China (nos. 30770530, 11032012, 11102240 and 11272365), the Fundamental Research Funds for the Central University of China (no. CDJXS11232243), and the Natural Science Foundation Project of CQ CSTC (2010bb5236).

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  1. Chengyu Zou

    Present address: Graduate School of Systemic Neuroscience, LMU, Munich, Germany

Authors and Affiliations

  1. Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, People’s Republic of China

    Chengyu Zou, Qing Luo, Jian Qin, Yisong Shi, Li Yang & Guanbin Song

  2. The State Key Lab of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou, 310027, People’s Republic of China

    Bingfeng Ju

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  1. Chengyu Zou
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  2. Qing Luo
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Correspondence to Guanbin Song.

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Zou, C., Luo, Q., Qin, J. et al. Osteopontin Promotes Mesenchymal Stem Cell Migration and Lessens Cell Stiffness via Integrin β1, FAK, and ERK Pathways. Cell Biochem Biophys 65, 455–462 (2013). https://doi.org/10.1007/s12013-012-9449-8

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  • DOI: https://doi.org/10.1007/s12013-012-9449-8

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