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Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 309 - 310
1 May 2006
Jones L Yeoumans B Hungerford D Frondoza C
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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.


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 3 | Pages 448 - 458
1 Apr 2001
Jones LC Frondoza C Hungerford DS

The pathogenesis of aseptic loosening of total joint prostheses is not clearly understood. Two features are associated with loosened prostheses, namely, particulate debris and movement of the implant. While numerous studies have evaluated the cellular response to particulate biomaterials, few have investigated the influence of movement of the implant on the biological response to particles. Our aim was therefore to test the hypothesis that excessive mechanical stimulation of the periprosthetic tissues induces an inflammatory response and that the addition of particulate biomaterials intensifies this.

We allocated 66 adult Beagle dogs to four groups as follows: stable implants with (I) and without (II) particulate polymethylmethacrylate (PMMA) and moving implants with (III) and without (IV) particulate PMMA. They were then evaluated at 2, 4, 6, 12 and 24 weeks.

The stable implants were well tolerated and a thin, fibrous membrane of connective tissue was observed. There was evidence of positive staining in some cells for interleukin-6 (IL-6). Addition of particulate PMMA around the stable implants resulted in an increase in the fibroblastic response and positive staining for IL-6 and tumour necrosis factor-alpha (TNF-α). By contrast, movement of the implant resulted in an immediate inflammatory response characterised by large numbers of histiocytes and cytokine staining for IL-1ß, TNF-α and IL-6. Introduction of particulate PMMA aggravated this response. Animals with particulate PMMA and movement of the implant have an intense inflammatory response associated with accelerated bone loss.

Our results indicate that the initiation of the inflammatory response to biomaterial particles was much slower than that to gross mechanical instability. Furthermore, when there was both particulate debris and movement, there was an amplification of the adverse tissue response as evidenced by the presence of osteolysis and increases in the presence of inflammatory cells and their associated cytokines.