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.

Autor: van Gemert Y; Experimental Rheumatology, Radboud university medical center, Nijmegen, the Netherlands., Blom AB; Experimental Rheumatology, Radboud university medical center, Nijmegen, the Netherlands., Di Ceglie I; Experimental Rheumatology, Radboud university medical center, Nijmegen, the Netherlands., Walgreen B; Experimental Rheumatology, Radboud university medical center, Nijmegen, the Netherlands., Helsen M; Experimental Rheumatology, Radboud university medical center, Nijmegen, the Netherlands., Sloetjes A; Experimental Rheumatology, Radboud university medical center, Nijmegen, the Netherlands., Vogl T; Institute of Immunology, University of Münster, Germany., Roth J; Institute of Immunology, University of Münster, Germany., Kruisbergen NNL; Experimental Rheumatology, Radboud university medical center, Nijmegen, the Netherlands., Pieterman EJ; Metabolic Health Research, TNO, Leiden, the Netherlands., Princen HMG; Metabolic Health Research, TNO, Leiden, the Netherlands., van der Kraan PM; Experimental Rheumatology, Radboud university medical center, Nijmegen, the Netherlands., van Lent PLEM; Experimental Rheumatology, Radboud university medical center, Nijmegen, the Netherlands., van den Bosch MHJ; Experimental Rheumatology, Radboud university medical center, Nijmegen, the Netherlands. Electronic address: martijn.vandenbosch@radboudumc.nl.
Jazyk: angličtina
Zdroj: Osteoarthritis and cartilage [Osteoarthritis Cartilage] 2023 Jul; Vol. 31 (7), pp. 934-943. Date of Electronic Publication: 2023 Mar 08.
DOI: 10.1016/j.joca.2023.01.577
Abstrakt: Introduction: The association between metabolic syndrome (MetS) and osteoarthritis (OA) development has become increasingly recognized. In this context, the exact role of cholesterol and cholesterol-lowering 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 × 10 -10 , 95% CI: -398.3 to -152.1; P = 2.1 × 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.
(Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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