DOES CYCLIC LOADING ALTER THE RESPONSE OF OSTEOBLAST-LIKE CELLS TO DEXAMETHASONE?

Abstract

Introduction: The response of osteoblasts to dexamethasone is dose-dependent. While low doses are used to stimulate osteoblasts to maintain their phenotype, high doses are cytotoxic. The purpose of this study was to test the hypothesis that mechanical stimulation alters the response of osteoblast-like cells to dexamethasone.

Materials & Methods: MG-63 cells were propagated on 6-well Flexcell plates (flexible silicone membranes) under standard culture conditions. One half of the plates were subjected to biaxial strain at a frequency of 0.5 Hz through an imposed vacuum pressure of -7kPa (~1% stretch; 0.01 strain) for 42 hours using the Flexercell Apparatus. Replicate samples were maintained under static conditions. Simultaneously, the cells were exposed to either 0, .001, .01, or .1 nM of dexamethasone. The wells were then spiked with tritiated thymidine for 6 hours. The results were normalized to the control values. Triplicate wells were included for each experimental condition; and the experiment was repeated four times. Data were analyzed by JMP statistical package (SAS).

Results: Increasing doses of dexamethasone resulted in decreasing cellular proliferation. For the unflexed cells, we noted the following reduction in proliferative capacity: 0.86% ± 0.09 (.001nM), 0.50% ± 0.07 (.01nM), and 0.39% ± 0.07 (.1nM). Similar results were observed for the cells exposed to cyclic loading: 0.89% ± 0.12 (.001nM), 0.52% ± 0.08 (.01nM), and 0.47% ± 0.07 (.1nM).

Discussion: Our results confirmed the work of others that there is a decrease in the proliferation of osteoblasts (incubated under static conditions) when exposed to high levels of dexamethasone. Although cyclic loading had no effect on the proliferative response of osteoblasts to dexamethasone, it may still have had an effect on cellular metabolism or function, which remains to be evaluated.