dc.creatorCórdova Jara, Luis
dc.creatorTrichet, V.
dc.creatorEscriou, V.
dc.creatorRosset, P.
dc.creatorAmiaud, J.
dc.creatorBattaglia, S.
dc.creatorCharrier, C.
dc.creatorBerreur, M.
dc.creatorBrion, R.
dc.creatorGouin, F.
dc.creatorLayrolle, P.
dc.creatorPassuti, N.
dc.creatorHeymann, D.
dc.date.accessioned2015-08-12T15:13:39Z
dc.date.available2015-08-12T15:13:39Z
dc.date.created2015-08-12T15:13:39Z
dc.date.issued2015
dc.identifierActa Biomaterialia 13 (2015) 150–158
dc.identifier1742-7061
dc.identifierDOI: 10.1016/j.actbio.2014.10.042
dc.identifierhttps://repositorio.uchile.cl/handle/2250/132635
dc.description.abstractReceptor activator of nuclear factor kappa-B (RANK) and RANK-ligand are relevant targets for the treatment of polyethylene particle-induced osteolysis. This study assessed the local administration of siRNA, targeting both human RANK and mouse Rank transcripts in a mouse model. Four groups of mice were implanted with polyethylene (PE) particles in the calvaria and treated locally with 2.5, 5 and 10 lg of RANK siRNA or a control siRNA delivered by the cationic liposome DMAPAP/DOPE. The tissues were harvested at day 9 after surgery and evaluated by micro-computed tomography, tartrate-resistant acid phosphatase (TRAP) immunohistochemistry for macrophages and osteoblasts, and gene relative expression of inflammatory and osteolytic markers. 10 lg of RANK siRNA exerted a protective effect against PE particleinduced osteolysis, decreasing the bone loss and the osteoclastogenesis, demonstrated by the significant increase in the bone volume (P < 0.001) and by the reduction in both the number of TRAP+ cells and osteoclast activity (P < 0.01). A bone anabolic effect demonstrated by the formation of new trabecular bone was confirmed by the increased immunopositive staining for osteoblast-specific proteins. In addition, 5 and 10 lg of RANK siRNA downregulated the expression of pro-inflammatory cytokines (P < 0.01) without depletion of macrophages. Our findings show that RANK siRNA delivered locally by a synthetic vector may be an effective approach for reducing osteolysis and may even stimulate bone formation in aseptic loosening of prosthetic implants.
dc.languageen
dc.publisherElsevier
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile
dc.subjectsiRNA
dc.subjectPolyethylene particle-induced osteolysis
dc.subjectWear debris
dc.subjectOsteoclast
dc.titleInhibition of osteolysis and increase of bone formation after local administration of siRNA-targeting RANK in a polyethylene particle-induced osteolysis model
dc.typeArtículo de revista


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