Inhibition of osteolysis and increase of bone formation after local administration of siRNA-targeting RANK in a polyethylene particle-induced osteolysis model

Autor: Pierre Layrolle, Régis Brion, Luis A. Córdova, Valérie Trichet, Virginie Escriou, Martine Berreur, Séverine Battaglia, Philippe Rosset, François Gouin, Jérôme Amiaud, Céline Charrier, N Passuti, Dominique Heymann
Přispěvatelé: Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Small interfering RNA
Osteolysis
EFFICIENT
Biochemistry
PATHWAY
Mice
0302 clinical medicine
Cationic liposome
RNA
Small Interfering
MACROPHAGES
Tartrate-resistant acid phosphatase
DECREASE
0303 health sciences
PERIPROSTHETIC OSTEOLYSIS
SMALL INTERFERING RNA
biology
Receptor Activator of Nuclear Factor-kappa B
WEAR PARTICLES
General Medicine
Isoenzymes
medicine.anatomical_structure
[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system
Polyethylene
030220 oncology & carcinogenesis
ZOLEDRONIC ACID
Immunohistochemistry
Biotechnology
Materials science
Acid Phosphatase
Genetic Vectors
Biomedical Engineering
Calvaria
Biomaterials
03 medical and health sciences
DELIVERY
Osteoclast
medicine
Animals
Humans
Molecular Biology
030304 developmental biology
Osteoblasts
Tartrate-Resistant Acid Phosphatase
Acid phosphatase
NECROSIS-FACTOR-ALPHA
medicine.disease
Disease Models
Animal
HEK293 Cells
[SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology
Gene Expression Regulation
Liposomes
Cancer research
biology.protein
Biomedical engineering
Zdroj: Acta Biomaterialia
Acta Biomaterialia, Elsevier, 2015, 13, pp.150-158. ⟨10.1016/j.actbio.2014.10.042⟩
Europe PubMed Central
ISSN: 1742-7061
DOI: 10.1016/j.actbio.2014.10.042⟩
Popis: International audience; 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 mg 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 mu g of RANK siRNA exerted a protective effect against PE particle-induced 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 mu g 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. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Databáze: OpenAIRE
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