Title
Osteoarthritis development is induced by increased dietary cholesterol and can be inhibited by atorvastatin in APOE*3Leiden.CETP mice, a translational model for atherosclerosis
Author
Gierman, L.M.
Kühnast, S.
Koudijs, A.
Pieterman, E.J.
Kloppenburg, M.
van Osch, G.J.V.M.
Stojanovic-Susulic, V.
Huizinga, T.W.J.
Princen, H.M.G.
Zuurmond. A.M.,
Publication year
2014
Abstract
Objective Hypercholesterolaemia, a risk factor for atherosclerosis (ATH), has been suggested to have a role in the development of osteoarthritis (OA). To test this hypothesis, the effect of cholesterol and different cholesterol-lowering treatments on OA was investigated in a mouse model resembling human lipoprotein metabolism. Methods Female ApolipoproteinE*3Leiden.human Cholesteryl Ester Transfer Protein mice received a westerntype diet with 0.1% (w/w) cholesterol (LC), 0.3% (w/w) cholesterol alone (HC) or treated with 3 mg/kg/day atorvastatin or 0.3 mg/kg/day ezetimibe. One group remained on chow (control). After 39 weeks, OA grades of the knees and the extent of ATH were determined. Plasma cholesterol levels were measured throughout the study. Results LC and HC groups developed significantly more OA at the medial side than the control group in a dosedependent manner. Atorvastatin but not ezetimibe treatment significantly suppressed OA development. As expected, features of ATH were significantly increased in the LC and HC groups compared with the control group and suppressed by atorvastatin (48%) and ezetimibe (55%) treatment. There were significant correlations between the development of OA on the medial side of the joint and cholesterol exposure (r=0.4) or ATH features (r=0.3). Conclusions Dietary cholesterol and accordingly increased plasma levels play a role in the development of OA. The correlation found between OA, cholesterol and ATH demonstrates that these variables are connected, but indicates the contribution of other ongoing processes in the development of OA. The suppressive effect on OA development of atorvastatin but not of ezetimibe, which had similar cholesterol exposure levels, corroborates these findings.
Subject
Alanine aminotransferase
Apolipoprotein E
Atorvastatin
Cholesterol ester transfer protein
Endothelial leukocyte adhesion molecule 1
Etimibe
Monocyte chemotactic protein 1
Serum amyloid A
Very low density lipoprotein
Animal experiment
Animal model
Animal tissue
Atherosclerosis
Cholesterol blood level
Cholesterol intake
Controlled study
Female
Knee osteoarthritis
Mouse
Nonhuman
Priority journal
Transgenic mouse
Biomedical Innovation
Healthy Living
Life
MHR - Metabolic Health Research
EELS - Earth, Environmental and Life Sciences
To reference this document use:
http://resolver.tudelft.nl/uuid:38012c33-28d8-40ac-a6e1-effe5bec01f9
DOI
https://doi.org/10.1136/annrheumdis-2013-203248
TNO identifier
472048
Source
Annals of the Rheumatic Diseases, 73 (73), 921-927
Document type
article