OP0129 Ldl Cholesterol-Accumulation during Experimental OA Leads to Increased Synovial Thickening and Ectopic Bone Formation, While Excessive Cholesterol Levels Shift the Balance towards Cartilage Destruction. (10th June 2014)

• Record Type: Journal Article
• Authors: De Munter, W.; van den Bosch, M.H.; Slöetjes, A.W.; van der Kraan, P.M.; van den Berg, W.B.; van Lent, P.L.
• Is Part Of: Annals of the rheumatic diseases. Volume 73:Supplement 2(2014)
• Page Start: 109
• Page End: 110
• Publication Date: 2014-06-10
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2014-eular.2489
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: A relation between osteoarthritis (OA) and the metabolic syndrome has long been established. One of the characteristics of the metabolic syndrome is increased cholesterol levels. In a recent study, we showed that LDL accumulation by LDL receptor deficient mice resulted in increased ectopic bone formation during experimental osteoarthritis [1]. Objectives: In the present study we investigate OA pathology in ApoE deficient (ApoE –/– ) mice with and without a cholesterol-rich diet, which is a model for extremely high systemic LDL cholesterol levels. Methods: Wild type (WT) and ApoE –/– mice received a normal or cholesterol-rich diet for 54 days. At day 18, experimental OA was induced by intra-articular injection of collagenase and animals were sacrificed at day 28 and 54. Joint pathology was investigated by histology. LDL levels were measured in serum and synovial wash-outs. Results: ApoE –/– mice on a normal diet showed markedly higher LDL levels than WT mice (8.90 mmol/L and 0.40 mmol/L, respectively; p<0.001). While no differences between the two groups were found at the early time point (day 28), end point OA (day 54) in ApoE –/– mice showed a strong increase of ectopic bone formation, mainly at the medial collateral ligament (fold increase 5.4; p<0.001) compared to WT mice. No significant differences in cartilage damage were found between the two groups, a slight increase in synovial thickening, however, was found in ApoE –/– mice (1.9 versus 1.1 in WT mice; p<0.05), suggesting an activated status of synovial lining cells. In addition, we investigated whether a cholesterol-rich diet could increase joint pathology after induction of OA. The diet increased LDL levels even more in ApoE –/– mice (fold increase 2.1, compared to ApoE –/– mice on a normal diet; p<0.001) and already at day 28, histological differences between the two groups were observed. Synovial thickening was four times increased (p<0.001) and also ectopic bone formation in the medial collateral ligament was strongly increased at this early time point (fold increase 2.7; p<0.01). Interestingly, the addition of a cholesterol-rich diet to ApoE –/– mice did not enhance ectopic bone formation at day 54 and even decreased it by 40% in the medial collateral ligament compared to ApoE –/– mice on normal diet. On the other hand, cartilage damage at the medial side of the femoral chondile was strongly increased compared to ApoE –/– on normal diet (fold increase 1.6; p<0.05). Conclusions: LDL cholesterol accumulation by ApoE deficiency or a cholesterol-rich diet results in increased synovial thickening and ectopic bone formation in experimental OA. Excessive LDL levels induced by a combination of ApoE deficiency and a cholesterol-rich diet unexpectedly decrease ectopic bone formation, but increase cartilage damage at end stage OA. References: de Munter et al. Arthritis Research & Therapy 2013, 15:R175. Disclosure of Interest: None declared DOI: 10.1136/annrheumdis-2014-eular.2489