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First published online 27 January 2009
doi: 10.1242/jcs.036293

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Mechanically induced osteogenic differentiation – the role of RhoA, ROCKII and cytoskeletal dynamics

¹ Bone and Joint R&D Center, VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304, USA
² Stanford University, Department of Bioengineering, Stanford, CA 94305, USA
³ Stanford University, Department of Mechanical Engineering, Stanford, CA 94305, USA
⁴ Columbia University, Department of Biomedical Engineering, New York, NY 10027, USA

^* Author for correspondence (e-mail: emily.arnsdorf{at}gmail.com)

Accepted 23 October 2008

Many biochemical factors regulating progenitor cell differentiation have been examined in detail; however, the role of the local mechanical environment on stem cell fate has only recently been investigated. In this study, we examined whether oscillatory fluid flow, an exogenous mechanical signal within bone, regulates osteogenic, adipogenic or chondrogenic differentiation of C3H10T1/2 murine mesenchymal stem cells by measuring Runx2, PPAR and SOX9 gene expression, respectively. Furthermore, we hypothesized that the small GTPase RhoA and isometric tension within the actin cytoskeleton are essential in flow-induced differentiation. We found that oscillatory fluid flow induces the upregulation of Runx2, Sox9 and PPAR, indicating that it has the potential to regulate transcription factors involved in multiple unique lineage pathways. Furthermore, we demonstrate that the small GTPase RhoA and its effector protein ROCKII regulate fluid-flow-induced osteogenic differentiation. Additionally, activated RhoA and fluid flow have an additive effect on Runx2 expression. Finally, we show RhoA activation and actin tension are negative regulators of both adipogenic and chondrogenic differentiation. However, an intact, dynamic actin cytoskeleton under tension is necessary for flow-induced gene expression.

Key words: Osteogenic differentiation, Mechanotransduction, Fluid flow, Mesenchymal stem cell

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				E. J. Arnsdorf, P. Tummala, R. Y. Kwon, and C. R. Jacobs Mechanically induced osteogenic differentiation - the role of RhoA, ROCKII and cytoskeletal dynamics Development, March 1, 2009; 136(5): e1 - e1. [Full Text]