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
Authors: W. De Munter, M.H. van den Bosch, A.W. Slöetjes, P.M. van der Kraan, W.B. van den Berg, P.L. van Lent
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> 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]. <h3>Objectives</h3> In the present study we investigate OA pathology in ApoE deficient (ApoE<sup>–/–</sup>) mice with and without a cholesterol-rich diet, which is a model for extremely high systemic LDL cholesterol levels. <h3>Methods</h3> Wild type (WT) and ApoE<sup>–/–</sup> 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. <h3>Results</h3> ApoE<sup>–/–</sup> mice on a normal diet showed markedly higher LDL levels than WT mice (8.90 mmol/L and 0.40 mmol/L, respectively; p&lt;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<sup>–/–</sup> mice showed a strong increase of ectopic bone formation, mainly at the medial collateral ligament (fold increase 5.4; p&lt;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<sup>–/–</sup> mice (1.9 versus 1.1 in WT mice; p&lt;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<sup>–/–</sup> mice (fold increase 2.1, compared to ApoE<sup>–/–</sup> mice on a normal diet; p&lt;0.001) and already at day 28, histological differences between the two groups were observed. Synovial thickening was four times increased (p&lt;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&lt;0.01). Interestingly, the addition of a cholesterol-rich diet to ApoE<sup>–/–</sup> mice did not enhance ectopic bone formation at day 54 and even decreased it by 40% in the medial collateral ligament compared to ApoE<sup>–/–</sup> mice on normal diet. On the other hand, cartilage damage at the medial side of the femoral chondile was strongly increased compared to ApoE<sup>–/–</sup> on normal diet (fold increase 1.6; p&lt;0.05). <h3>Conclusions</h3> 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. <h3>References</h3> de Munter et al. Arthritis Research &amp; Therapy 2013, 15:R175. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2489