IL-1β inhibition combined with cholesterol-lowering therapies decreases synovial lining thickness and spontaneous cartilage degeneration in a humanized dyslipidemia mouse model

被引：7

作者：

van Gemert, Y. ^{[1
]}

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

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

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

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

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

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

van Lent, P. L. E. M. ^{[1
,3
]}

机构：

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

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

[3] Radboud Univ Nijmegen Med Ctr, Geert Grootepl 28, NL-6525 GA Nijmegen, Netherlands

来源：

OSTEOARTHRITIS AND CARTILAGE | 2023年 / 31卷 / 03期

关键词：

Osteoarthritis; Metabolic syndrome; Systemic inflammation; Cholesterol; IL-1; Animal model; KNEE OSTEOARTHRITIS; STATIN USE; METABOLIC SYNDROME; MICE; INFLAMMATION; NLRP3; ATHEROSCLEROSIS; ASSOCIATION; PROGRESSION;

D O I：

10.1016/j.joca.2022.09.014

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: Both systemic inflammation and dyslipidemia contribute to osteoarthritis (OA) develop-ment and have been suggested as a possible link between metabolic disease and OA development. Recently, the CANTOS trial showed a reduction in knee and hip replacements after inhibition of IL-1 beta in patients with a history of cardiovascular disease and high inflammatory risk. In this light, we investigated whether inhibition of IL-1 beta combined with cholesterol-lowering therapies can reduce OA development in dyslipidemic APOE*3Leiden mice under pro-inflammatory dietary conditions.Materials and methods: Female ApoE3*Leiden mice were fed a cholesterol-supplemented Western-Type diet (WTD) for 38 weeks. After 14 weeks, cholesterol-lowering and anti-inflammatory treatments were started. Treatments included atorvastatin alone or with an anti-IL1 beta antibody, and atorvastatin combined with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor alirocumab without or with the anti-IL1 beta antibody. Knee joints were analyzed for cartilage degradation, synovial inflammation and ectopic bone formation using histology at end point.Results: Cholesterol-lowering treatment successfully decreased systemic inflammation in dyslipidemic mice, which was not further affected by inhibition of IL-1 beta. Synovial thickening and cartilage degener-ation were significantly decreased in mice that received cholesterol-lowering treatment combined with inhibition of IL-1 beta (P < 0.01, P < 0.05, respectively) compared to mice fed a WTD alone. Ectopic bone formation was comparable between all groups.Conclusion: These results indicate that inhibition of IL-1 beta combined with cholesterol-lowering therapy diminishes synovial thickening and cartilage degeneration in mice and may imply that this combination therapy could be beneficial in patients with metabolic inflammation.(c) 2022 The Authors. 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：340 / 350

页数：11