title: Proinflammatory mediator expression in a novel murine model of titanium-particle-induced intramedullary inflammation.
abstract: Wear debris from total joint replacement prostheses is implicated in periprosthetic osteolysis and implant loosening. The pathophysiology of this biological process remains unclear. Animal models of particle-induced osteolysis have proven useful in the study of specific tissue responses to wear debris. However, existing in vivo murine models of particle-mediated inflammation do not permit analysis of cortical bone degradation. This study describes a murine model of particle disease using an intramedullary rod in the mouse femur to parallel the clinical situation. The model consists of placing a 10-mm-long Kirschner wire retrograde in both femurs of C57b1/6 male mice via a medial parapatellar arthrotomy. Phagocytosable titanium particles were also implanted unilaterally to replicate generation of wear debris. Mice were sacrificed at 2, 10, and 26 weeks and whole femurs were cultured for 72 h. Levels of interleukin-6, monocyte chemotactic protein-1, and macrophage colony stimulating factor were assayed by ELISA. Transverse histological sections, at the level of the implant, were taken and stained with hematoxylin and eosin (H&E). Results demonstrated increased expression of proinflammatory mediators at 2 weeks in femora with rod and particles compared to femora with rods alone. Destruction of the endosteum was evident at 2, 10, and 26 weeks in the femora with titanium. This novel murine model of particle-induced intramedullary inflammation may facilitate cost-effective genetic studies and offers investigators a simple, clinically relevant intramedullary model to readily examine the pathogenesis of particle-mediated periprosthetic osteolysis.
authors.affiliation: Department of Orthopaedic Surgery, Stanford University School of Medicine, California, USA.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Warme
authors.forename: Noah J
authors.initials: NJ
authors.lastname: Epstein
authors.forename: Michael C D
authors.initials: MC
authors.lastname: Trindade
authors.forename: Keita
authors.initials: K
authors.lastname: Miyanishi
authors.forename: Ting
authors.initials: T
authors.lastname: Ma
authors.forename: Ramin R
authors.initials: RR
authors.lastname: Saket
authors.forename: Donald
authors.initials: D
authors.lastname: Regula
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
authors.forename: R Lane
authors.initials: RL
authors.lastname: Smith
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D018932:Chemokine CCL2 / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology*; D006651:Histocytochemistry; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D051379:Mice; D009924:Organ Culture Techniques; D010014:Osteolysis / Q000000981:diagnostic imaging / Q000473:pathology*; D019736:Prostheses and Implants; D011859:Radiography; D013193:Stainless Steel; D014025:Titanium / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D001672:Biocompatible Materials; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D013193:Stainless Steel; D016173:Macrophage Colony-Stimulating Factor; D014025:Titanium