title: Anti-inflammatory and chondroprotective effects of atorvastatin in a cartilage explant model of osteoarthritis.
abstract: 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.
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, 243 122, UP, India.
authors.forename: Nitya N
authors.initials: NN
authors.lastname: Pathak
authors.forename: Madhu C
authors.initials: MC
authors.lastname: Lingaraju
authors.forename: Venkanna
authors.initials: V
authors.lastname: Balaganur
authors.forename: Vinay
authors.initials: V
authors.lastname: Kant
authors.forename: Amar S
authors.initials: AS
authors.lastname: More
authors.forename: Dhirendra
authors.initials: D
authors.lastname: Kumar
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
authors.forename: Surendra K
authors.initials: SK
authors.lastname: Tandan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000069059:Atorvastatin / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D006025:Glycosaminoglycans / Q000378:metabolism; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000009:adverse effects; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010003:Osteoarthritis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D006025:Glycosaminoglycans; D053583:Interleukin-1beta; D020011:Protective Agents; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000069059:Atorvastatin; D053509:Matrix Metalloproteinase 13