HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/3/C776    most recent 00082.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Riddle, R. C. Articles by Donahue, H. J. Search for Related Content PubMed PubMed Citation Articles by Riddle, R. C. Articles by Donahue, H. J.

RECEPTORS AND SIGNAL TRANSDUCTION

MAP kinase and calcium signaling mediate fluid flow-induced human mesenchymal stem cell proliferation

¹Division of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania; and ²Orthopaedics Research Laboratories, School of Medicine, University of California at Davis, Davis, California

Submitted 25 February 2005 ; accepted in final form 27 October 2005

Mechanical signals are important regulators of skeletal homeostasis, and strain-induced oscillatory fluid flow is a potent mechanical stimulus. Although the mechanisms by which osteoblasts and osteocytes respond to fluid flow are being elucidated, little is known about the mechanisms by which bone marrow-derived mesenchymal stem cells respond to such stimuli. Here we show that the intracellular signaling cascades activated in human mesenchymal stem cells by fluid flow are similar to those activated in osteoblastic cells. Oscillatory fluid flow inducing shear stresses of 5, 10, and 20 dyn/cm² triggered rapid, flow rate-dependent increases in intracellular calcium that pharmacological studies suggest are inositol trisphosphate mediated. The application of fluid flow also induced the phosphorylation of extracellular signal-regulated kinase-1 and -2 as well as the activation of the calcium-sensitive protein phosphatase calcineurin in mesenchymal stem cells. Activation of these signaling pathways combined to induce a robust increase in cellular proliferation. These data suggest that mechanically induced fluid flow regulates not only osteoblastic behavior but also that of mesenchymal precursors, implying that the observed osteogenic response to mechanical loading may be mediated by alterations in the cellular behavior of multiple members of the osteoblast lineage, perhaps by a common signaling pathway.

mechanotransduction; bone; marrow

This article has been cited by other articles:

				D. H. Craig, B. Haimovich, and M. D. Basson {alpha}-Actinin-1 phosphorylation modulates pressure-induced colon cancer cell adhesion through regulation of focal adhesion kinase-Src interaction Am J Physiol Cell Physiol, December 1, 2007; 293(6): C1862 - C1874. [Abstract] [Full Text] [PDF]

				A. F. Taylor, M. M. Saunders, D. L. Shingle, J. M. Cimbala, Z. Zhou, and H. J. Donahue Mechanically stimulated osteocytes regulate osteoblastic activity via gap junctions Am J Physiol Cell Physiol, January 1, 2007; 292(1): C545 - C552. [Abstract] [Full Text] [PDF]