Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 91, Issue -, Pages 208-219Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2017.04.093
Keywords
NF-kappa B; Inflammation; Celastrol; Intervertebral disc degeneration
Funding
- National Nature Foundation of China [81371988, 81401871, 81401162]
- Zhejiang Provincial Natural Science Foundation of China [LY17H060010, LY15H060008]
- Major scientific and technological project of medical and health in Zhejiang Province [WKJ-ZJ-1527]
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Celastrol has been reported to exert therapeutic potential on pro-inflammatory diseases including asthma, Crohn's disease, arthritis and neurodegenerative disorders via inhibiting NF-kappa B pathway. While the effect of celastrol on intervertebral disc degeneration (IDD), which is also a pro-inflammatory disease, remains unknown. In this study, we evaluated the effect of celastrol on IDD in IL-1 beta treated human nucleus pulposus cells in vitro as well as in puncture induced rat IDD model in vivo. Our results showed that celastrol reduced the expression of catabolic genes (MMP-3, 9, 13, ADAMTS-4, 5), oxidative stress factors (COX-2, iNOS) and pro-inflammatory factors (IL-6, TNF-a) induced by IL-1 beta in nucleus pulposus cells, also phosphorylation of IkB alpha and p65 were attenuated by celastrol, indicating NF-kappa B pathway was inhibited by celastrol in nucleus pulposus cells. In vivo study showed that celastrol treated rats had stronger T2-weighted signal than vehicle-treated rats at 2 weeks and 6 weeks' time point, suggesting celastrol could attenuate intervertebral disc degeneration in vivo. Together, our study demonstrates that celastrol could reduce IL-1 beta induced matrix catabolism, oxidative stress and inflammation in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration in vivo, which shows its potential to be a therapeutic drug for IDD. (C) 2017 Elsevier Masson SAS. All rights reserved.
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