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 .
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.
de Munter et al. Arthritis Research & Therapy 2013, 15:R175.
Disclosure of Interest None declared
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