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

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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.

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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

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

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Authors and Affiliations

  1. Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, 243 122, UP, India

    Nitya N. Pathak, Madhu C. Lingaraju, Venkanna Balaganur, Vinay Kant, Amar S. More, Dhirendra Kumar, Dinesh Kumar & Surendra K. Tandan

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  1. Nitya N. Pathak
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  2. Madhu C. Lingaraju
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  3. Venkanna Balaganur
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Correspondence to Surendra K. Tandan.

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Pathak, N.N., Lingaraju, M.C., Balaganur, V. et al. Anti-inflammatory and chondroprotective effects of atorvastatin in a cartilage explant model of osteoarthritis. Inflamm. Res. 64, 161–169 (2015). https://doi.org/10.1007/s00011-014-0794-5

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