UHMWPE wear debris upregulates mononuclear cell proinflammatory gene expression in a novel murine model of intramedullary particle disease

BACKGROUND: We examined the effects of ultra-high molecular weight polyethylene (UHMWPE) particles on mononuclear cell proinflammatory gene expression in a novel murine model. We hypothesized that mononuclear cell gene transcription of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), interleukin-6 (IL-6) and macrophage chemoattractant protein-1 (MCP-1) would be upregulated by the addition of polyethylene particles in this murine intramedullary rod model. MATERIAL AND METHODS: The model involved a stainless steel Kirschner wire inserted retrograde with a line-to-line fit in bilateral femora of C57bl/6 mice. Additionally, the right femora were injected with 3 x 10(9) UHMWPE particles. Mononuclear marrow cells were isolated by bone marrow aspiration and Ficoll-Paque centrifugation at 2, 4 and 10 weeks post-surgery. Total RNA was isolated and real-time RT-PCR was performed to quantify gene expression. Histological specimens of explanted femora were also analyzed to track the changes in periprosthetic tissue. RESULTS: UHMWPE particles stimulated gene transcription in mononuclear cells when examined at 2, 4 and 10 weeks post-surgery, compared to the rod-only group. Relative levels of IL-1beta and MCP-1 mRNA increased in a linear fashion over the 10-week time-course. IL-6 mRNA showed increased expression which peaked at 4 weeks. TNF-alpha mRNA expression was variable and reached a minimum at 4 weeks. The addition of UHMWPE particles stimulated ingress of macrophages and multinuclear cells of macrophage origin to the bone-implant interface. INTERPRETATION: In this model, a single bolus of UHMWPE particles had a long-term effect on gene transcription in mononuclear cells which perpetuated a chronic inflammatory state. This murine model of intramedullary particle-induced inflammation simulates periprosthetic events associated with implant wear in humans, and may contribute to a more mechanistic understanding of wear-debris associated prosthesis failure.