title: Wear-particle-induced osteoclast osteolysis: the role of particulates and mechanical strain.
abstract: Periprosthetic osteolysis involves osteoclast activation by wear particulates and their exposure to mechanical perturbation through exposure to shear forces generated by periprosthetic fluid as well as interface micromotion. This study aimed to determine the interactions between wear particulates, mechanical stimulation, and osteoclasts. In static cultures, wear particulates increased osteoclast differentiation. Addition of neutralizing antibodies to RANKL (receptor activator of nuclear factor kappa ligand) inhibited the particle-induced increase in osteoclast numbers. Cyclic 5000 microstrains were applied with the use of a custom-built device to marrow-derived cultures to assess the effect on osteoclast differentiation. Mechanical strain application alone decreased osteoclast differentiation, which was further decreased by the addition of particles despite increases in the soluble RANKL to osteoprotegerin (OPG) ratio. Mechanical strain alone induced mature osteoclast apoptosis in a dose-dependent manner. In contrast, in the mature osteoclast model, the addition of nonmetal particulates protected the osteoclasts from becoming apoptopic. Titanium (Ti) and cobalt chromium (CoCr) particles, however, induced osteoclast apoptosis, whereas polyethylene (PE) and polymethylmethacrylate (PMMA) did not. Wear particulates and mechanical stimulation interact via an eicosanoid-dependent pathway to alter osteoclast function and survival. The addition of mechanical perturbation to a particle-laden system thus appears to enhance the potential for osteolytic activity by enhancing osteoclast survival.
authors.affiliation: Department of Biomedical Engineering, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia B3H 3J5, Canada.
authors.forename: Robyn A
authors.initials: RA
authors.lastname: MacQuarrie
authors.forename: Ying
authors.initials: Y
authors.lastname: Fang Chen
authors.forename: Chad
authors.initials: C
authors.lastname: Coles
authors.forename: Gail I
authors.initials: GI
authors.lastname: Anderson
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001853:Bone Marrow / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002858:Chromium Alloys / Q000494:pharmacology; D015777:Eicosanoids / Q000037:antagonists & inhibitors / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects* / Q000473:pathology*; D010014:Osteolysis / Q000139:chemically induced* / Q000473:pathology*; D053244:Osteoprotegerin; D010316:Particle Size; D010969:Plastics; D020959:Polyethylene / Q000494:pharmacology; D053245:RANK Ligand; D011817:Rabbits; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D012995:Solubility; D013314:Stress, Mechanical; D013499:Surface Properties; D014025:Titanium / Q000494:pharmacology
chemical_list: D000906:Antibodies; D002352:Carrier Proteins; D002858:Chromium Alloys; D015777:Eicosanoids; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D010969:Plastics; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D020959:Polyethylene; D014025:Titanium