Hypercholesterolemia boosts joint destruction in chronic arthritis. An experimental model aggravated by foam macrophage infiltration
EntityUAM. Departamento de Medicina
10.1186/ar4261Arthritis Research & Therapy 15.4 (2013): 81
ISSN1478-6354 (print); 1478-6362 (online)
Funded byThis work was supported by research grants from Instituto de Salud Carlos III (PS09/01625, GH-B and PS09/00034, RL). IP-P is the recipient of a fellowship from Fundacion Conchita Rábago. MJM-C and RG are both recipients of a Sara Borrell contract from Instituto de Salud Carlos III. RL was funded by Instituto de Salud Carlos III through a research staff stabilization program
SubjectsHypercholesterolemia; Osteoprotegerin; Chronic arthritis,; Medicina
Rights© 2013 Prieto-Potín et al.; licensee BioMed Central Ltd.
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
Objective: The aim of this study was to determine whether hypercholesterolemia increases articular damage in a rabbit model of chronic arthritis. Methods: Hypercholesterolemia was induced in 18 rabbits by administrating a high-fat diet (HFD). Fifteen rabbits were fed normal chow as controls. Chronic antigen-induced arthritis (AIA) was induced in half of the HFD and control rabbits, previously immunized, by intra-articular injections of ovalbumin. After sacrifice, lipid and systemic inflammation markers were analyzed in blood serum. Synovium was analyzed by Krenn score, multinucleated cell counting, immunohistochemistry of RAM11 and CD31, and TNF-a and macrophage chemoattractant protein-1 (MCP-1) gene expression. Active bone resorption was assessed by protein expression of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and quantification of cathepsin K, contact surface and the invasive area of pannus into bone. Results: Rabbits receiving the HFD showed higher total serum cholesterol, HDL, triglycerides and CRP levels than rabbits fed a normal diet. Synovitis score was increased in HFD, and particularly in AIA and AIA + HFD groups. AIA + HFD synovium was characterized by a massive infiltration of RAM11+ cells, higher presence of multinucleated foam cells and bigger vascularization than AIA. Cathepsin K+ osteoclasts and the contact surface of bone resorbing pannus were also increased in rabbits with AIA + HFD compared with AIA alone. Synovial TNF-a and MCP-1 gene expression was increased in AIA and HFD rabbits compared with healthy animals. RANKL protein expression in AIA and AIA + HFD groups was higher compared with either HFD or normal groups. Conclusions: This experimental model demonstrates that hypercholesterolemia increments joint tissue damage in chronic arthritis, with foam macrophages being key players in this process.
Google Scholar:Prieto-Potín, Ivan - Roman-Blas, Jorge A. - Martínez Calatrava, María José - Gómez, Rodolfo - Largo, Raquel - Herrero-Beaumont, Gabriel
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Little, Robert D.; Prieto-Potin, Iván; Pérez-Baos, Sandra; Villalvilla, Amanda; Gratal, Paula; Cicuttini, Flavia; Largo, Raquel; Herrero-Beaumont, Gabriel
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Martínez-Calatrava, M. J.; Largo, R.; Prieto-Potín, I.; Herrero-Beaumont, Gabriel