Anti-inflammatory and chondroprotective effects of atorvastatin in a cartilage explant model of osteoarthritis
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This study aimed to assess the chondroprotective potential of atorvastatin in rat’s cartilage explant culture model of osteoarthritis, stimulated by interleukin-1β (IL-1β).
Materials and methods
The cartilage explants were treated with 20 ng/ml IL-1β alone or with 20 ng/ml IL-1β + various concentration of atorvastatin (1, 3, or 10 µM dissolved in DMSO) and incubated at 37 °C for 24 h. Also, control (0.25 % DMSO), stimulated (20 ng IL-1β) and treatment (atorvastatin 10 µM) cartilage explants were incubated without and with 1400W (10 µM). After 24 h of incubation, TNF-α, PGE2, MMP-13, TIMP-1, NO, and superoxide anion formation (O2 −) concomitant with glycosaminoglycans (GAGs) were estimated in the medium.
Atorvastatin inhibited IL-1β-induced GAGs release, TNF-α, MMP-13, and O2 − with no effect on TIMP-1 and NO. In addition, the source of NO in normal and atorvastatin-treated cartilage was eNOS, while for IL-1β-stimulated cartilage it was iNOS. The cartilage degradation was associated with the combined effects of increased NO and O2 − rather than only NO.
The present study suggests that atorvastatin has the ability to protect cartilage degradation following IL-1β-stimulated cartilage in in vitro OA model and supports additional therapeutic application of atorvastatin in OA.
KeywordsCartilage explants Proinflammatory cytokines MMP-13/TIMP-1 Reactive oxygen species 1400W Atorvastatin
Tissue inhibitors of matrix metalloproteinases
Tumor necrosis factor-α
1, 9-dimethylmethylene blue
Reactive oxygen species
Conflict of interest
All authors declare that they have no conflicts of interest concerning this article.
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