10/26/2013 1 Cholesterol accumulation in synovial lining macrophages results in ectopic bone formation during experimental osteoarthritis W de Munter, AB Blom, MM Helsen, B Walgreen, PM van der Kraan, LAB Joosten, WB van den Berg, PLEM van Lent Department of Experimental Rheumatology, Radboud university medical center 2013 ACR Annual Meeting Disclosure We have no competing interests Osteoarthritis (OA) Introduction – Experimental Design – Results – Conclusions Not only a disease of the cartilage, also synovial involvement. Synovium Joint cavity Cartilage Fibroblast Macrophage Chondrocyte Synovial macrophages and OA • Essential for cartilage destruction during experimental OA. 1 • Important players in driving inflammatory and destructive responses in OA. 2 • Crucial for osteophyte formation (ectopic bone formation at cartilage margins) and enthesophyte formation (ectopic bone in tendons or ligaments). 3 1Blom et al., 2007 2 Bondeson et al., 2010 3 van Lent et al., 2004 Introduction – Experimental Design – Results – Conclusions Modified LDL and macrophages • In an inflammatory milieu, LDL can be modified. 1 • Increased LDL levels will therefore result in enhanced oxLDL levels during inflammatory processes. 2 • OxLDL is taken up by macrophages via SR-A and CD36. 3-5 • OxLDL uptake can change the phenotype of macrophages. 3-5 1Morel et al., 1983 2 Badimon et al., 2011 3 Groeneweg et al., 2006 4 van Tits et al., 2011 5 Jiang et al., 2012 Introduction – Experimental Design – Results – Conclusions Hypothesis Introduction – Experimental Design – Results – Conclusions
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HIGH SERUM-CHOLESTEROL LEVELS BY EITHER LOW DENSITY ...
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10/26/2013
1
Cholesterol accumulation in synovial lining
macrophages results in ectopic bone formation
during experimental osteoarthritis
W de Munter, AB Blom, MM Helsen, B Walgreen, PM van der Kraan, LAB Joosten,
Acknowledgements Radboud university medical center Department of Experimental Rheumatology Therapeutics: Peter van Lent, PhD Arjen Blom, PhD Peter van der Kraan, PhD Annet Slöetjes, BSc Birgitte Walgreen, BSc Monique Helsen, BSc Wim van den Berg, PhD Department of Medicine and Nijmegen Institute for Infection, Inflammation and Immunity: Leo Joosten, PhD Leiden University Medical Center Department of Molecular Cell Biology:
Peter ten Dijke, PhD University of Muenster (DEU) Intitute of Immunology: Thomas Vogl, PhD Johannes Roth, PhD [email protected]