title: Polyethylene wear particles induce TLR 2 upregulation in the synovial layer of mice.
abstract: A cellular and receptor mediated response to ultra-high-molecular-weight-polyethylene (UHMWPE) wear particles results in a release of proinflammatory cytokines and induces an inflammatory reaction causing osteolysis in total joint replacement. This investigation offers insight into the toll-like receptor (TLR) mediated activation by polyethylene wear particles in the synovial layer of mice. We hypothesized that, similar to recent in vitro results, UHMWPE particles lead to an upregulation of TLR 1 and 2 and TLR 4 in vivo in the synovial tissue of mice as well. Therefore, UHMWPE particles were generated in a common knee simulator according to the ISO standard, separated by acid digestion and determined by scanning electron microscopy. Endotoxin was removed using a method based on ultracentrifugation. A particle suspension (50 μl; 0.1 vol./vol.%) was injected into the left knee joint of female Balb/c mice (n = 8). In a control group, phosphate-buffered saline was injected into the left knee of Balb/c mice (n = 8). The mice were sacrificed after 7 days. Immunohistochemical staining was performed with TLR 1, 2 and 4 polyclonal antibodies for Balb/c mice and evaluated by light microscopy. The particle-stimulated group showed a thickened synovial layer, an increased cellular infiltration and a TLR 2-upregulation in the synovial layer compared to the control group. An increased expression of TLR 1 and TLR 4 could not be demonstrated. These results indicate a mainly TLR 2-induced inflammation to polyethylene wear debris in the synovial layer of mice.
authors.affiliation: Department of Orthopaedic Surgery, University Hospital of Munich (LMU), Campus Großhadern, Marchioninistr. 15, 81377, Munich, Germany, alexander.paulus@med.uni-muenchen.de.
authors.forename: A C
authors.initials: AC
authors.lastname: Paulus
authors.forename: J
authors.initials: J
authors.lastname: Frenzel
authors.forename: A
authors.initials: A
authors.lastname: Ficklscherer
authors.forename: B P
authors.initials: BP
authors.lastname: Roßbach
authors.forename: C
authors.initials: C
authors.lastname: Melcher
authors.forename: V
authors.initials: V
authors.lastname: Jansson
authors.forename: S
authors.initials: S
authors.lastname: Utzschneider
mesh_terms: D000818:Animals; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D020959:Polyethylene / Q000737:chemistry*; D013583:Synovial Membrane / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D020959:Polyethylene