dc.creator | Córdova Jara, Luis | |
dc.creator | Trichet, V. | |
dc.creator | Escriou, V. | |
dc.creator | Rosset, P. | |
dc.creator | Amiaud, J. | |
dc.creator | Battaglia, S. | |
dc.creator | Charrier, C. | |
dc.creator | Berreur, M. | |
dc.creator | Brion, R. | |
dc.creator | Gouin, F. | |
dc.creator | Layrolle, P. | |
dc.creator | Passuti, N. | |
dc.creator | Heymann, D. | |
dc.date.accessioned | 2015-08-12T15:13:39Z | |
dc.date.available | 2015-08-12T15:13:39Z | |
dc.date.created | 2015-08-12T15:13:39Z | |
dc.date.issued | 2015 | |
dc.identifier | Acta Biomaterialia 13 (2015) 150–158 | |
dc.identifier | 1742-7061 | |
dc.identifier | DOI: 10.1016/j.actbio.2014.10.042 | |
dc.identifier | https://repositorio.uchile.cl/handle/2250/132635 | |
dc.description.abstract | Receptor 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.language | en | |
dc.publisher | Elsevier | |
dc.rights | http://creativecommons.org/licenses/by-nc-nd/3.0/cl/ | |
dc.rights | Atribución-NoComercial-SinDerivadas 3.0 Chile | |
dc.subject | siRNA | |
dc.subject | Polyethylene particle-induced osteolysis | |
dc.subject | Wear debris | |
dc.subject | Osteoclast | |
dc.title | Inhibition of osteolysis and increase of bone formation after local administration of siRNA-targeting RANK in a polyethylene particle-induced osteolysis model | |
dc.type | Artículo de revista | |