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Tensile Strain as a Regulator of Mesenchymal Stem Cell Osteogenesis

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Abstract

A role for mechanical stimulation in the control of cell fate has been proposed and mechanical conditioning of mesenchymal stem cells (MSCs) is of interest in directing MSC behavior for tissue engineering applications. This study investigates strain-induced differentiation and proliferation of MSCs, and investigates the cellular mechanisms of mechanotransduction. MSCs were seeded onto a collagen-coated silicone substrate and exposed to cyclic tensile mechanical strain of 2.5% at 0.17 Hz for 1–14 days. To examine mechanotransduction, cells were strained in the presence of the stretch-activated cation channel (SACC) blocker, gadolinium chloride (GdCl3); the extracellular regulated kinase (ERK) inhibitor, U0126; the p38 inhibitor, SB203580; and the phosphatidylinosito1 3-kinase (PI3-kinase) inhibitor, LY294002. Following exposure to strain, the osteogenic markers Cbfα1, collagen type I, osteocalcin, and BMP2 were temporally expressed. Exposure to strain in the presence of GdCl3 (10 μM) reduced the induction of collagen I expression, thus identifying a role for SACC, at least in part, as mechanosensors in strain-induced MSC differentiation. The strain-induced synthesis of BMP2 was found to be reduced by inhibitors of the kinases, ERK, p38, and PI3 kinase. Additionally, mechanical strain reduced the rate of MSC proliferation. The identification of the mechanical control of MSC proliferation and the molecular link between mechanical stimulation and osteogenic differentiation has consequences for regenerative medicine through the development of a functional tissue engineering approach.

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Acknowledgments

This study was supported by a grant under the Program for Research in Third Level Institutions (PRTLI) to the Trinity Centre for Bioengineering.

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Authors and Affiliations

  1. Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin, Dublin 2, Ireland

    E. M. Kearney, E. Farrell, P. J. Prendergast & V. A. Campbell

  2. Department of Physiology, School of Medicine, Trinity College Dublin, Dublin 2, Ireland

    V. A. Campbell

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  1. E. M. Kearney
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  2. E. Farrell
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Associate Editor Sean S. Kohles oversaw the review of this article.

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Kearney, E.M., Farrell, E., Prendergast, P.J. et al. Tensile Strain as a Regulator of Mesenchymal Stem Cell Osteogenesis. Ann Biomed Eng 38, 1767–1779 (2010). https://doi.org/10.1007/s10439-010-9979-4

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