TY - JOUR
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.
N1 - Publisher Copyright:
© 2015, Springer Basel.
PY - 2015/3/13
Y1 - 2015/3/13
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.
KW - 1400W
KW - Atorvastatin
KW - Cartilage explants
KW - MMP-13/TIMP-1
KW - Proinflammatory cytokines
KW - Reactive oxygen species
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U2 - 10.1007/s00011-014-0794-5
DO - 10.1007/s00011-014-0794-5
M3 - Article
C2 - 25596949
AN - SCOPUS:84925534690
SN - 1023-3830
VL - 64
SP - 161
EP - 169
JO - Inflammation Research
JF - Inflammation Research
IS - 3-4
ER -