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

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 97/1/135    most recent 01260.2003v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted 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 (17) Citing Articles via Google Scholar Google Scholar Articles by Ponik, S. M. Articles by Pavalko, F. M. Search for Related Content PubMed PubMed Citation Articles by Ponik, S. M. Articles by Pavalko, F. M.

Formation of focal adhesions on fibronectin promotes fluid shear stress induction of COX-2 and PGE₂ release in MC3T3-E1 osteoblasts

Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana 46202

Submitted 24 November 2003 ; accepted in final form 27 February 2004

Mechanical loading of bone is important for the structural integrity of the skeleton and the maintenance of bone mass. Mechanically loading bone generates fluid shear stress (FSS) across the surface of bone cells resulting in the induction of cyclooxygenase-2 (COX-2) and release of prostaglandins, both of which are necessary for mechanically induced bone formation. However, the mechanisms by which cells transduce FSS-induced signals across the membrane and into the cell remain poorly understood. Focal adhesions, which are specialized sites of attachment between cells and the extracellular matrix, play a role in signal transduction and have been proposed to function as mechanosensors. To directly test whether focal adhesions mediate mechanotransduction in bone cells, we inhibited the formation of focal adhesions by 1) culturing MC3T3-E1 osteoblasts on bovine serum albumin (BSA), which does not contain integrin binding sites or by 2) treating cells cultured on fibronectin with soluble Arg-Gly-Asp-Ser (RGDS) peptide to specifically block integrin-fibronectin interactions. We then subjected the cells to FSS and measured COX-2 induction and PGE₂ release. Both COX-2 induction and PGE₂ release in response to FSS were significantly decreased when osteoblasts were treated with soluble RGDS peptide compared with controls. However, RGDS peptide treatment did not affect FSS-induced ERK phosphorylation. Interestingly, osteoblasts cultured on BSA to suppress focal adhesion formation secreted fibronectin and increased focal adhesion formation over time, which correlated with the induction of COX-2 in response to FSS. Together, these results suggest that fibronectin-induced formation of focal adhesions promotes FSS-induced PGE₂ release and upregulation of COX-2 protein.

integrins; bone; mechanical loading; cyclooxygenase-2; prostaglandin E₂; metabolism

This article has been cited by other articles:

				J. M. Tarbell and E. E. Ebong The Endothelial Glycocalyx: A Mechano-Sensor and -Transducer Sci. Signal., October 7, 2008; 1(40): pt8 - pt8. [Abstract] [Full Text] [PDF]

				E. F. Morgan, R. E. Gleason, L. N. M. Hayward, P. L. Leong, and K. T. S. Palomares Mechanotransduction and Fracture Repair J. Bone Joint Surg. Am., February 1, 2008; 90(Supplement_1): 25 - 30. [Abstract] [Full Text] [PDF]

				A. M. D. Malone, C. T. Anderson, P. Tummala, R. Y. Kwon, T. R. Johnston, T. Stearns, and C. R. Jacobs Primary cilia mediate mechanosensing in bone cells by a calcium-independent mechanism PNAS, August 14, 2007; 104(33): 13325 - 13330. [Abstract] [Full Text] [PDF]

				J. W. Triplett and F. M. Pavalko Disruption of {alpha}-actinin-integrin interactions at focal adhesions renders osteoblasts susceptible to apoptosis Am J Physiol Cell Physiol, November 1, 2006; 291(5): C909 - C921. [Abstract] [Full Text] [PDF]

				K.-H. W. Lau, S. Kapur, C. Kesavan, and D. J. Baylink Up-regulation of the Wnt, Estrogen Receptor, Insulin-like Growth Factor-I, and Bone Morphogenetic Protein Pathways in C57BL/6J Osteoblasts as Opposed to C3H/HeJ Osteoblasts in Part Contributes to the Differential Anabolic Response to Fluid Shear J. Biol. Chem., April 7, 2006; 281(14): 9576 - 9588. [Abstract] [Full Text] [PDF]

				J. Zaric and C. Ruegg Integrin-mediated Adhesion and Soluble Ligand Binding Stabilize COX-2 Protein Levels in Endothelial Cells by Inducing Expression and Preventing Degradation J. Biol. Chem., January 14, 2005; 280(2): 1077 - 1085. [Abstract] [Full Text] [PDF]