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J Appl Physiol (March 5, 2004). doi:10.1152/japplphysiol.01260.2003
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Submitted on November 24, 2003
Accepted on February 27, 2004

Formation of Focal Adhesions on Fibronectin Promotes Fluid Shear Stress Induction of COX-2 and PGE2 Release in MC3T3-E1 Osteoblasts

Suzanne M Ponik1 and Fredrick M Pavalko1*

1 Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, USA

* To whom correspondence should be addressed. E-mail: fpavalko{at}iupui.edu.

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 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 block integrin-fibronectin interactions. We then subjected the cells to FSS and measured COX-2 induction and PGE2 release. COX-2 induction and PGE2 release in response to FSS were significantly decreased when osteoblasts were treated with soluble RGDS peptide compared to controls. However, RGDS peptide treatment did not affect FSS-induced ERK phosphorylation. Interestingly, osteoblasts cultured on BSA to suppress focal adhesion formation increased both fibronectin secretion and focal adhesion formation over time which correlated with the induction of COX-2 in response to FSS. Together, these results suggest that fibronectin-induced focal adhesion formation promotes FSS-induced PGE2 release and upregulation of COX-2 protein.




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