文摘
A relation between osteoarthritis (OA) and increased cholesterol levels is apparent. In the present study we investigate OA pathology in apolipoprotein E (ApoE)p>−p>p>/−p> mice with and without a cholesterol-rich diet, a model for high systemic low density lipoprotein (LDL) cholesterol levels independent of weight.p>
Method
<p id="abspara0015">Wild type (WT), Apoep>−p>p>/−p>, S100a9p>−/−p> and Apoep>−p>p>/−p>S100a9p>−/−p> mice (C57BL/6 background) received a standard or cholesterol-rich diet. Experimental OA was induced by intra-articular injection of collagenase and animals were sacrificed at day 10 and day 36.p>Results
<p id="abspara0020">Although minimal differences in cartilage damage were found between the WT and ApoEp>−p>p>/−p> mice, increased synovial thickening was found in the latter. Thirty-six days after OA-induction, ApoEp>−p>p>/−p> mice on a standard diet showed increased ectopic bone formation, particularly at the medial collateral ligament, compared with OA in WT mice. Furthermore, a significant increase in synovial gene expression of both S100a8 and S100a9 and S100A8/S100A9 protein levels was found in ApoEp>−p>p>/−p> mice, suggesting an activated inflammatory status of synovial cells.p><p id="abspara0025">In both ApoEp>−p>p>/−p> and WT mice, addition of a cholesterol-rich diet resulted in excessive bone formation in the medial collateral ligament at late-time-point OA. Interestingly, at the early time point, proteoglycan deposition was already significantly increased in ApoEp>−p>p>/−p> mice compared with WT mice. Mice deficient for both ApoE and S100a9 also showed increased ectopic bone formation, but not synovial activation, suggesting a role for S100-proteins in cholesterol-mediated synovial activation.p>Conclusions
<p id="abspara0030">Increased cholesterol levels strongly elevate synovial activation and ectopic bone formation in early-stage collagenase-induced OA.