Intensive cholesterol-lowering treatment reduces synovial inflammation during early collagenase-induced osteoarthritis, but not pathology at end-stage disease in female dyslipidemic E3L.CETP mice

被引：3

作者：

van Gemert, Y. ^{[1
]}

Blom, A. B. ^{[1
]}

Di Ceglie, I. ^{[1
]}

Walgreen, B. ^{[1
]}

Helsen, M. ^{[1
]}

Sloetjes, A. ^{[1
]}

Vogl, T. ^{[3
]}

Roth, J. ^{[3
]}

Kruisbergen, N. N. L. ^{[1
]}

Pieterman, E. J. ^{[2
]}

Princen, H. M. G. ^{[2
]}

van der Kraan, P. M. ^{[1
]}

van Lent, P. L. E. M. ^{[1
]}

van den Bosch, M. H. J. ^{[1
]}

机构：

[1] Radboud Univ Nijmegen Med Ctr, Expt Rheumatol, Nijmegen, Netherlands

[2] TNO, Metab Hlth Res, Leiden, Netherlands

[3] Univ Munster, Inst Immunol, Munster, Germany

来源：

OSTEOARTHRITIS AND CARTILAGE | 2023年 / 31卷 / 07期

关键词：

Osteoarthritis; Metabolic syndrome; Cholesterol; Cholesterol-lowering treatment; Animal model; STATIN USE; KNEE OSTEOARTHRITIS; METABOLIC SYNDROME; ASSOCIATION; PROGRESSION; ATHEROSCLEROSIS; METAANALYSIS; ALIROCUMAB; MODEL; DIET;

D O I：

10.1016/j.joca.2023.01.577

中图分类号：

R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学（修复外科学）];

学科分类号：

摘要：

Introduction: The association between metabolic syndrome (MetS) and osteoarthritis (OA) development has become increasingly recognized. In this context, the exact role of cholesterol and cholesterollowering therapies in OA development has remained elusive. Recently, we did not observe beneficial effects of intensive cholesterol-lowering treatments on spontaneous OA development in E3L.CETP mice. We postulated that in the presence of local inflammation caused by a joint lesion, cholesterol-lowering therapies may ameliorate OA pathology.Materials and methods: Female ApoE3*Leiden.CETP mice were fed a cholesterol-supplemented Western type diet. After 3 weeks, half of the mice received intensive cholesterol-lowering treatment consisting of atorvastatin and the anti-PCSK9 antibody alirocumab. Three weeks after the start of the treatment, OA was induced via intra-articular injections of collagenase. Serum levels of cholesterol and triglycerides were monitored throughout the study. Knee joints were analyzed for synovial inflammation, cartilage degeneration, subchondral bone sclerosis and ectopic bone formation using histology. Inflammatory cytokines were determined in serum and synovial washouts.Results: Cholesterol-lowering treatment strongly reduced serum cholesterol and triglyceride levels. Mice receiving cholesterol-lowering treatment showed a significant reduction in synovial inflammation (P = 0.008, WTD: 95% CI: 1.4- 2.3; WTD + AA: 95% CI: 0.8- 1.5) and synovial lining thickness (WTD: 95% CI: 3.0-4.6, WTD + AA: 95% CI: 2.1-3.2) during early-stage collagenase-induced OA. Serum levels of S100A8/A9, MCP-1 and KC were significantly reduced after cholesterol-lowering treatment (P = 0.0005, 95% CI: -46.0 to -12.0; P = 2.8 x 10-10, 95% CI: -398.3 to -152.1; P = 2.1 x 10-9, -66.8 to -30.4, respectively). However, this reduction did not reduce OA pathology, determined by ectopic bone formation, subchondral bone sclerosis and cartilage damage at end-stage disease.Conclusion: This study shows that intensive cholesterol-lowering treatment reduces joint inflammation after induction of collagenase-induced OA, but this did not reduce end stage pathology in female mice.& COPY; 2023 The Author(s). Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/).

引用

页码：934 / 943

页数：10

共 1 条

[1] A single dose of anti-IL-1β antibodies prevents Western diet-induced immune activation during early stage collagenase-induced osteoarthritis, but does not ameliorate end-stage pathology
Kruisbergen, N. N. L.
van Gemert, Y.
Walgreen, B.
Helsen, M. M. A.
Sloetjes, A. W.
Koenders, M. I.
van de Loo, F. A. J.
Roth, J.
Vogl, T.
van der Kraan, P. M.
Blom, A. B.
van den Bosch, M. H. J.
van Lent, P. L. E. M.
OSTEOARTHRITIS AND CARTILAGE, 2021, 29 (10) : 1462 - 1473

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