Title
IL-1β inhibition combined with cholesterol-lowering therapies decreases synovial lining thickness and spontaneous cartilage degeneration in a humanized dyslipidemia mouse model
Author
van Gemert, Y.
Kruisbergen, N.N.L.
Blom, A.B.
van den Bosch, M.H.J.
van der Kraan, P.M.
Pieterman, E.J.
Princen, H.M.G.
van Lent, P.L.E.M.
Publication year
2023
Abstract
Introduction: Both systemic inflammation and dyslipidemia contribute to osteoarthritis (OA) development 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-1β in patients with a history of cardiovascular disease and high inflammatory risk. In this light, we investigated whether inhibition of IL-1β 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-IL1β antibody, and atorvastatin combined with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor alirocumab without or with the anti-IL1β 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-1β. Synovial thickening and cartilage degeneration were significantly decreased in mice that received cholesterol-lowering treatment combined with inhibition of IL-1β (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-1β 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.
Subject
Animal model
Cholesterol
IL-1β
Metabolic syndrome
Osteoarthritis
Systemic inflammation
To reference this document use:
http://resolver.tudelft.nl/uuid:1a2f7d24-2e72-4030-8162-ea7021287ce9
DOI
https://doi.org/10.1016/j.joca.2022.09.014
TNO identifier
980187
Source
Osteoarthritis and Cartilage, 31 (31), 340-350
Document type
article