Hypercholesterolemia boosts joint destruction in chronic arthritis. An experimental model aggravated by foam macrophage infiltration
Arthritis Research & Therapy 2013, 15:R81 doi:10.1186/ar4261Published: 13 August 2013
To study whether hypercholesterolemia increases articular damage in a rabbit model of chronic arthritis.
Hypercholesterolemia was induced in eighteen rabbits by administrating a high-fat diet (HFD). Fifteen rabbits were fed normal chow as controls. Chronic 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-alpha and MCP-1 gene expression. Active bone resorption was assessed by protein expression of RANKL, OPG and quantification of cathepsin K, contact surface and invasive area of pannus into bone.
Rabbits receiving HFD showed higher total serum cholesterol, HDL, triglycerides and CRP levels than rabbits fed 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 contact surface of bone resorbing pannus were also increased in rabbits with AIA+HFD compared with AIA alone. Synovial TNF-alpha 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.
This experimental model demonstrates that hypercholesterolemia increments joint tissue damage in chronic arthritis, being foam macrophages key players in this process.