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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)161-169
Number of pages9
JournalInflammation Research
Volume64
Issue number3-4
DOIs
StatePublished - 2015
Externally publishedYes

Fingerprint

Osteoarthritis
Cartilage
Interleukin-1
Anti-Inflammatory Agents
Tissue Inhibitor of Metalloproteinase-1
Dimethyl Sulfoxide
Glycosaminoglycans
Matrix Metalloproteinases
Atorvastatin Calcium
Dinoprostone
Superoxides

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Immunology

Cite this

Pathak, N. N., Lingaraju, M. C., Balaganur, V., Kant, V., More, A. S., Kumar, D., ... Tandan, S. K. (2015). Anti-inflammatory and chondroprotective effects of atorvastatin in a cartilage explant model of osteoarthritis. Inflammation Research, 64(3-4), 161-169. https://doi.org/10.1007/s00011-014-0794-5

Anti-inflammatory and chondroprotective effects of atorvastatin in a cartilage explant model of osteoarthritis. / Pathak, Nitya N.; Lingaraju, Madhu C.; Balaganur, Venkanna; Kant, Vinay; More, Amar S.; Kumar, Dhirendra; Kumar, Dinesh; Tandan, Surendra K.

In: Inflammation Research, Vol. 64, No. 3-4, 2015, p. 161-169.

Research output: Contribution to journalArticle

Pathak, NN, Lingaraju, MC, Balaganur, V, Kant, V, More, AS, Kumar, D, Kumar, D & Tandan, SK 2015, 'Anti-inflammatory and chondroprotective effects of atorvastatin in a cartilage explant model of osteoarthritis', Inflammation Research, vol. 64, no. 3-4, pp. 161-169. https://doi.org/10.1007/s00011-014-0794-5
Pathak, Nitya N. ; Lingaraju, Madhu C. ; Balaganur, Venkanna ; Kant, Vinay ; More, Amar S. ; Kumar, Dhirendra ; Kumar, Dinesh ; Tandan, Surendra K. / Anti-inflammatory and chondroprotective effects of atorvastatin in a cartilage explant model of osteoarthritis. In: Inflammation Research. 2015 ; Vol. 64, No. 3-4. pp. 161-169.
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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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T1 - Anti-inflammatory and chondroprotective effects of atorvastatin in a cartilage explant model of osteoarthritis

AU - Pathak, Nitya N.

AU - Lingaraju, Madhu C.

AU - Balaganur, Venkanna

AU - Kant, Vinay

AU - More, Amar S.

AU - Kumar, Dhirendra

AU - Kumar, Dinesh

AU - Tandan, Surendra K.

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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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KW - MMP-13/TIMP-1

KW - Proinflammatory cytokines

KW - Reactive oxygen species

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