Artículo de revista
Inhibition of osteolysis and increase of bone formation after local administration of siRNA-targeting RANK in a polyethylene particle-induced osteolysis model
Fecha
2015Registro en:
Acta Biomaterialia 13 (2015) 150–158
1742-7061
DOI: 10.1016/j.actbio.2014.10.042
Autor
Córdova Jara, Luis
Trichet, V.
Escriou, V.
Rosset, P.
Amiaud, J.
Battaglia, S.
Charrier, C.
Berreur, M.
Brion, R.
Gouin, F.
Layrolle, P.
Passuti, N.
Heymann, D.
Institución
Resumen
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.