title: Pro-osteoclastic in vitro effect of Polyethylene-like nanoparticles: Involvement in the pathogenesis of implant aseptic loosening.
abstract: Polyethylene micro-sized wear particles released from orthopedic implants promote inflammation and osteolysis; however, less is known about the bioactivity of polyethylene nanosized wear particles released from the last generation of polymer-bearing surfaces. We aim to assess the internalization of fluorescent polyethylene-like nanoparticles by both human macrophages and osteoclasts and also, to determine their effects in osteoclastogenesis in vitro. Human macrophages and osteoclasts were incubated with several ratios of fluorescent polyethylene-like nanoparticles between 1 and 72 h, and 4 h, 2, 4, 6, and 9 days, respectively. The internalization of nanoparticles was quantified by flow cytometry and followed by both confocal and video time-lapse microscopy. Osteoclast differentiation and activity was semiquantified by tartrate-resistant acid phosphatase (TRAP) staining, TRAP mRNA relative expression, and pit resorption assay, respectively. Macrophages, osteoclast precursors and mature osteoclasts internalized nanoparticles in a dose- and time-dependent manner and maintained their resorptive activity. In addition, nanoparticles significantly increased the osteoclastogenesis as shown by upregulation of the TRAP expressing cell number. We conclude that polyethylene-like nanosized wear particles promote osteoclast differentiation without alteration of bone resorptive activity of mature osteoclasts and they could be considered as important actors in periprosthetic osteolysis of the last new generation of polymer-bearing surfaces. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2649-2657, 2016.
authors.affiliation: Laboratory of Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumours, INSERM, UMR 957, Nantes, 44035, France.|University of Nantes, Nantes Atlantique Universities, Nantes, France.|Nantes University Hospital, Nantes, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Brulefert
authors.affiliation: Laboratory of Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumours, INSERM, UMR 957, Nantes, 44035, France. lcordova@stanford.edu.|University of Nantes, Nantes Atlantique Universities, Nantes, France. lcordova@stanford.edu.|Department of Oral and Maxillofacial Surgery-Faculty of Dentistry, University of Chile-Conicyt, Santiago, Chile. lcordova@stanford.edu.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Córdova
authors.affiliation: Laboratory of Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumours, INSERM, UMR 957, Nantes, 44035, France.|University of Nantes, Nantes Atlantique Universities, Nantes, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Brulin
authors.affiliation: CEISAM-UMR CNRS 6230, University of Nantes, Nantes, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Faucon
authors.affiliation: Nantes University Hospital, Nantes, France.|MicroPICell Platform, SFR Santé François Bonamy, INSERM, UMS 016-UMS CNRS 3556, Nantes, France.
authors.forename: Philipe
authors.initials: P
authors.lastname: Hulin
authors.affiliation: Nantes University Hospital, Nantes, France.|MicroPICell Platform, SFR Santé François Bonamy, INSERM, UMS 016-UMS CNRS 3556, Nantes, France.
authors.forename: Steven
authors.initials: S
authors.lastname: Nedellec
authors.affiliation: Laboratory of Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumours, INSERM, UMR 957, Nantes, 44035, France.|University of Nantes, Nantes Atlantique Universities, Nantes, France.|Nantes University Hospital, Nantes, France.
authors.forename: François
authors.initials: F
authors.lastname: Gouin
authors.affiliation: Laboratory of Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumours, INSERM, UMR 957, Nantes, 44035, France.|University of Nantes, Nantes Atlantique Universities, Nantes, France.|Nantes University Hospital, Nantes, France.
authors.forename: Norbert
authors.initials: N
authors.lastname: Passuti
authors.affiliation: CEISAM-UMR CNRS 6230, University of Nantes, Nantes, France.
authors.forename: Eléna
authors.initials: E
authors.lastname: Ishow
authors.affiliation: Laboratory of Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumours, INSERM, UMR 957, Nantes, 44035, France.|University of Nantes, Nantes Atlantique Universities, Nantes, France.|Nantes University Hospital, Nantes, France.|Department of Oncology and Metabolism, University of Sheffield, The Medical School, Sheffield, England, United Kingdom.
authors.forename: Dominique
authors.initials: D
authors.lastname: Heymann
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D007595:Joint Prosthesis / Q000009:adverse effects*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D053758:Nanoparticles / Q000009:adverse effects* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D010014:Osteolysis / Q000188:drug therapy; D010316:Particle Size; D020959:Polyethylene / Q000009:adverse effects* / Q000378:metabolism; D011475:Prosthesis Failure; D000071681:Tartrate-Resistant Acid Phosphatase / Q000032:analysis / Q000378:metabolism
chemical_list: D020959:Polyethylene; C000605510:ACP5 protein, human; D000071681:Tartrate-Resistant Acid Phosphatase
keywords: aseptic loosening; macrophages; nanoparticles; osteoclasts; polyethylene