title: Macrophages and fibroblasts respond differently to PMMA particles and mechanical strain.
abstract: A primary factor limiting the long-term outcome of total joint arthroplasty is the aseptic loosening of prosthetic components. The bone-host interface of an unstable implant is associated with large quantities of wear debris as well as an altered mechanical environment. In vitro cellular studies on the effects of particulate biomaterials have been conducted under static conditions. The principal objective of this study was to test the hypothesis that the application of cyclic tensile strain to cultured macrophages and fibroblasts alters the response of these cells to particulate polymethylmethacrylate. P388D1 macrophages and three human synovial fibroblast cells were exposed to particulate PMMA (0, 0.4, 4.0, and 40.0 mg/well) (n = 3) and tested under static or dynamic [cyclic tensile strain (0.5 Hz, 0.2 strain)] conditions. Cellular proliferation was determined by autoradiography following 3H-thymidine incorporation. IL-1beta, TNF-alpha, and IL-6 were identified using immunocytochemistry. Exposure of macrophages to particulate PMMA and/or cyclic tensile strain resulted in a decrease in DNA synthesis. Neither treatment altered the proliferative capacity of fibroblasts. Macrophages and fibroblasts stained positively for IL-1beta, TNF-alpha, and IL-6 under all of the experimental conditions tested. Our study provides evidence that macrophages, but not fibroblasts, exhibit decreased proliferative capacity when exposed to particulate PMMA and mechanical stimuli.
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD, USA. ljones3@jhmi.edu
authors.forename: Lynne C
authors.initials: LC
authors.lastname: Jones
authors.forename: Michelle
authors.initials: M
authors.lastname: Tucci
authors.forename: Carmelita
authors.initials: C
authors.lastname: Frondoza
mesh_terms: D001672:Biocompatible Materials / Q000008:administration & dosage; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008863:Microspheres; D010316:Particle Size; D019904:Polymethyl Methacrylate / Q000008:administration & dosage*; D013314:Stress, Mechanical
chemical_list: D001672:Biocompatible Materials; D019904:Polymethyl Methacrylate