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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
  1. W. De Munter,
  2. M.H. van den Bosch,
  3. A.W. Slöetjes,
  4. P.M. van der Kraan,
  5. W.B. van den Berg,
  6. P.L. van Lent
  1. Experimental Rheumatology, Radboud University Medical Center, Nijmegen, Netherlands


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.


  1. de Munter et al. Arthritis Research & Therapy 2013, 15:R175.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.2489

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