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Inflammation Research

, Volume 64, Issue 3–4, pp 161–169 | Cite as

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

  • Nitya N. Pathak
  • Madhu C. Lingaraju
  • Venkanna Balaganur
  • Vinay Kant
  • Amar S. More
  • Dhirendra Kumar
  • Dinesh Kumar
  • Surendra K. Tandan
Original Research Paper

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).

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.

Keywords

Cartilage explants Proinflammatory cytokines MMP-13/TIMP-1 Reactive oxygen species 1400W Atorvastatin 

Abbreviations

MMP

Matrix metalloproteinases

TIMP

Tissue inhibitors of matrix metalloproteinases

TNF-α

Tumor necrosis factor-α

IL-1β

Interleukin-1 beta

PGE2

Prostaglandin E2

NO

Nitric oxide

GAGs

Glycosaminoglycans

DMSO

Dimethyl sulfoxide

DMMB

1, 9-dimethylmethylene blue

MTT

Methylthiazolyldiphenyl-tetrazolium bromide

ROS

Reactive oxygen species

Notes

Conflict of interest

All authors declare that they have no conflicts of interest concerning this article.

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Copyright information

© Springer Basel 2015

Authors and Affiliations

  • Nitya N. Pathak
    • 1
  • Madhu C. Lingaraju
    • 1
  • Venkanna Balaganur
    • 1
  • Vinay Kant
    • 1
  • Amar S. More
    • 1
  • Dhirendra Kumar
    • 1
  • Dinesh Kumar
    • 1
  • Surendra K. Tandan
    • 1
  1. 1.Division of Pharmacology and ToxicologyIndian Veterinary Research InstituteBareillyIndia

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