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). 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. 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. CONCLUSION: 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.
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). 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. 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. CONCLUSION: 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.
Authors: Sawsan Youssef; Olaf Stüve; Juan C Patarroyo; Pedro J Ruiz; Jennifer L Radosevich; Eun Mi Hur; Manuel Bravo; Dennis J Mitchell; Raymond A Sobel; Lawrence Steinman; Scott S Zamvil Journal: Nature Date: 2002-11-07 Impact factor: 49.962
Authors: Bernard P Leung; Naveed Sattar; Anne Crilly; Morag Prach; David W McCarey; Helen Payne; Rajan Madhok; Carol Campbell; J Alastair Gracie; Foo Y Liew; Iain B McInnes Journal: J Immunol Date: 2003-02-01 Impact factor: 5.422
Authors: E J Dombrecht; J F Van Offel; C H Bridts; D G Ebo; V Seynhaeve; A J Schuerwegh; W J Stevens; L S De Clerck Journal: Clin Exp Rheumatol Date: 2007 Jul-Aug Impact factor: 4.473
Authors: M E Farkouh; J D Greenberg; R V Jeger; K Ramanathan; F W A Verheugt; J H Chesebro; H Kirshner; J S Hochman; C L Lay; S Ruland; B Mellein; P T Matchaba; V Fuster; S B Abramson Journal: Ann Rheum Dis Date: 2007-04-05 Impact factor: 19.103