Pathak Nitya N, Lingaraju Madhu C, Balaganur Venkanna, Kant Vinay, More Amar S, Kumar Dhirendra, Kumar Dinesh, Tandan Surendra K
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, 243 122, UP, India.
Inflamm Res. 2015 Apr;64(3-4):161-9. doi: 10.1007/s00011-014-0794-5. Epub 2015 Jan 18.
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).
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.
本研究旨在评估阿托伐他汀在白细胞介素 -1β(IL-1β)刺激的大鼠骨关节炎软骨外植体培养模型中的软骨保护潜力。
软骨外植体分别用20 ng/ml IL-1β单独处理,或用20 ng/ml IL-1β加不同浓度的阿托伐他汀(1、3或10 μM,溶于二甲基亚砜)处理,并在37°C孵育24小时。此外,对照(0.25%二甲基亚砜)、刺激(20 ng IL-1β)和处理(10 μM阿托伐他汀)的软骨外植体在有无1400W(10 μM)的情况下孵育。孵育24小时后,测定培养基中肿瘤坏死因子-α(TNF-α)、前列腺素E2(PGE2)、基质金属蛋白酶-13(MMP-13)、金属蛋白酶组织抑制因子-1(TIMP-1)、一氧化氮(NO)、超氧阴离子生成(O2(-))以及糖胺聚糖(GAGs)的含量。
阿托伐他汀抑制了IL-1β诱导的GAGs释放、TNF-α、MMP-13和O2(-),对TIMP-1和NO无影响。此外,正常和阿托伐他汀处理的软骨中NO的来源是内皮型一氧化氮合酶(eNOS),而IL-1β刺激的软骨中NO的来源是诱导型一氧化氮合酶(iNOS)。软骨降解与NO和O2(-)增加的联合作用有关,而不仅仅是NO。
本研究表明,在体外骨关节炎模型中,阿托伐他汀具有保护IL-1β刺激的软骨免受降解的能力,并支持阿托伐他汀在骨关节炎中的额外治疗应用。