title: UHMWPE wear debris upregulates mononuclear cell proinflammatory gene expression in a novel murine model of intramedullary particle disease.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopedic Surgery, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Noah J
authors.initials: NJ
authors.lastname: Epstein
authors.forename: William E
authors.initials: WE
authors.lastname: Bragg
authors.forename: Ting
authors.initials: T
authors.lastname: Ma
authors.forename: Joshua
authors.initials: J
authors.lastname: Spanogle
authors.forename: R Lane
authors.initials: RL
authors.lastname: Smith
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001862:Bone Resorption / Q000473:pathology*; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D005269:Femur / Q000473:pathology*; D015870:Gene Expression; D018836:Inflammation Mediators / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D011095:Polyethylenes; D019736:Prostheses and Implants; D013193:Stainless Steel; D013718:Tensile Strength; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D001672:Biocompatible Materials; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D011095:Polyethylenes; D014409:Tumor Necrosis Factor-alpha; D013193:Stainless Steel; D016173:Macrophage Colony-Stimulating Factor