title: Increased osteoclastic differentiation by PMMA particle-associated macrophages. Inhibitory effect by interleukin 4 and leukemia inhibitory factor.
abstract: To determine the influence of polymethylmethacrylate (PMMA) wear particles on macrophage-osteoclast differentiation, PMMA particles were added to mouse monocytes which were cocultured with UMR 106 osteoblast-like cells in the presence of 1,25 dihydroxy vitamin D3[1,25(OH)2D3] for up to 7 days on glass coverslips and for up to 14 days on human cortical bone slices. An increase in osteoclast differentiation, as evidenced by the expression of the osteoclast-associated enzyme tartrate-resistant acid phosphatase (TRAP) and the extent of lacunar bone resorption, was observed in monocyte cultures to which PMMA had been added. Interleukin 4 (IL-4) and Leukemia Inhibitory Factor (LIF) added to these cocultures caused considerably less expression of TRAP and significant inhibition of lacunar bone resorption. This inhibitory effect was reversed by the addition of specific neutralizing antibodies to LIF and IL-4. These findings show that PMMA-wear particle-associated macrophages exhibit an enhanced capacity for differentiation to osteoclastic bone-resorbing cells.
authors.affiliation: Nuffield Department of Orthopaedic Surgery, University of Oxford, Nuffield Orthopaedic Centre, Headington, UK.
authors.forename: A
authors.initials: A
authors.lastname: Sabokbar
authors.forename: Y
authors.initials: Y
authors.lastname: Fujikawa
authors.forename: J
authors.initials: J
authors.lastname: Brett
authors.forename: D W
authors.initials: DW
authors.lastname: Murray
authors.forename: N A
authors.initials: NA
authors.lastname: Athanasou
mesh_terms: D000135:Acid Phosphatase / Q000502:physiology; D000818:Animals; D014408:Biomarkers, Tumor / Q000502:physiology; D001862:Bone Resorption; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003343:Corrosion; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6; D007527:Isoenzymes / Q000502:physiology; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects*; D008768:Methylmethacrylates / Q000494:pharmacology*; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects* / Q000201:enzymology; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D014408:Biomarkers, Tumor; D006131:Growth Inhibitors; D015850:Interleukin-6; D007527:Isoenzymes; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D008768:Methylmethacrylates; D015847:Interleukin-4; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase