title: The potential role of human osteoblasts for periprosthetic osteolysis             following exposure to wear particles.
abstract: Aseptic loosening in total hip replacement is mainly caused by wear particles inducing inflammation and osteolysis. Wear can be a consequence of micromotions at the interface between implant and bone cement. Due to complex cellular interactions, different mediators (e.g. cytokines, proteinases) are released, which can promote osteolytic processes in the periprosthetic tissue followed by loosening of the implant. Furthermore, a reduced matrix synthesis and an induced apoptosis rate can be observed. The purpose of this study was to evaluate to what extent human primary osteoblasts exposed to wear particles are involved in the osteolysis. The viability, the secretion of collagen and collagenases and the variety of released cytokines after particle exposure was examined. Therefore, human osteoblasts were incubated with particles experimentally generated in the interface between hip stems with rough and smooth surface finishings as well as different material compositions (Ti-6Al-7Nb, Co-28Cr-6Mo and 316L) and bone cement mantle made of Palacos R containing zirconium oxide particles. Commercially pure titanium particles, titanium oxide, polymethylmethacrylate and particulate zirconium oxide were used as references. The results revealed distinct effects on the cytokine release of human osteoblasts towards particulate debris. Thereby, human osteoblasts released increased levels of interleukine (IL)-6 and IL-8 after treatment with metallic wear particles. The expression of VEGF was slightly induced by all particle entities at lower concentrations. Apoptotic rates were enhanced for osteoblasts exposed to all the tested particles. Furthermore, the de novo synthesis of type 1 collagen was reduced and the expression of the matrix metalloproteinase (MMP)-1 was considerably increased. However, wear particles of Co-28Cr-6Mo stems seemed to be more aggressive, whereas particles derived from stainless steel stems caused less adverse cellular reaction. Among the reference particles, which caused less altered reactions in the metabolism of osteoblasts in general, ZrO2 can be assumed as the material with the smallest cell biological effects.
authors.affiliation: Department of Orthopaedics, University of Rostock, D-18057 Rostock, Germany. katrin.lochner@med.uni-rostock.de
authors.forename: Katrin
authors.initials: K
authors.lastname: Lochner
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
authors.forename: Anika
authors.initials: A
authors.lastname: Jonitz
authors.forename: Doris
authors.initials: D
authors.lastname: Hansmann
authors.forename: Petra
authors.initials: P
authors.lastname: Mueller
authors.forename: Brigitte
authors.initials: B
authors.lastname: Mueller-Hilke
authors.forename: Rainer
authors.initials: R
authors.lastname: Bader
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D001672:Biocompatible Materials / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology; D001843:Bone Cements / Q000009:adverse effects; D018786:Bone Substitutes / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology; D024042:Collagen Type I / Q000032:analysis / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis; D016209:Interleukin-8 / Q000032:analysis / Q000096:biosynthesis; D008422:Materials Testing; D020781:Matrix Metalloproteinase 1 / Q000032:analysis / Q000096:biosynthesis; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010014:Osteolysis / Q000139:chemically induced / Q000517:prevention & control; D010316:Particle Size; D019904:Polymethyl Methacrylate / Q000009:adverse effects; D061251:Primary Cell Culture; D019736:Prostheses and Implants / Q000009:adverse effects; D013193:Stainless Steel / Q000009:adverse effects; D014025:Titanium / Q000009:adverse effects; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000096:biosynthesis; D015040:Zirconium / Q000009:adverse effects
chemical_list: D001672:Biocompatible Materials; D001843:Bone Cements; D018786:Bone Substitutes; D024042:Collagen Type I; D015850:Interleukin-6; D016209:Interleukin-8; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013193:Stainless Steel; C009495:titanium dioxide; D019904:Polymethyl Methacrylate; D015040:Zirconium; D014025:Titanium; D020781:Matrix Metalloproteinase 1; C028541:zirconium oxide