Abstract
Wear debris is a key factor in the pathophysiology of aseptic loosening of orthopaedic endoprostheses. Cobalt-chromium-molybdenum (Co-CrMo) alloys are used for metal-metal hip implants due to their enhanced wear resistance profiles. Whilst these alloys have widespread clinical application, little is known about their direct effect on osteoblast biology. To address this issue, in this study we have investigated particle-mediated inflammation, as a putative mechanism of aseptic loosening. The effects of Co2+ ions on the bone cellular milieu were assessed in vitro by profiling of classical inflammatory mediators. The inflammatory driver PGE2 was quantified and found to be increased, following osteoblast stimulation with metal ions, suggesting the initiation of a local inflammatory response to metal particle exposure. To determine the biological import of this molecular event, the role of metal ions in recruiting inflammatory cells by chemokine production was assessed. These data demonstrated significant induction of the chemokines, IL-8 and MCP-1 following both 12 and 24 hour exposure to 10ppm of Co2+. In this study, we demonstrate that Co2+ particles can rapidly induce chemotactic cytokines, IL-8 and MCP-1 early stress-responsive chemokines that function in activation and chemotaxis of monocytes, and PGE2, which stimulates bone resorption. We have shown that this induction occurs at a transcriptional level with significantly increased mRNA levels. These data lend further weight to the hypothesis that wear mediated osteolysis, is due, at least in part, to underlying chronic inflammation.
Correspondence should be addressed to Mr Carlos Wigderowitz, Senior Lecturer, University Department of Orthopaedic and Trauma Surgery, Ninewells Hospital and Medical School, Dundee DD1 9SY.
