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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.
Osteoarthritis and cartilage, March 2023, 2023-Mar, 2023-03-00, 20230301, Letnik: 31, Številka: 3Journal Article
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. 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. 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. 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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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