Anti-inflammatory and chondroprotective effects of atorvastatin in a cartilage explant model of osteoarthritis.

Objective: 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).

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.

Results: 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.

Conclusions: 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.