Celastrol reduces IL-1β induced matrix catabolism, oxidative stress and inflammation in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration in vivo
Authors: Xiao-Lei Zhang
Yu Chen
Yun-Tao Gu
Jiao-Xiang Chen
Jun-Jun Xie
Jian Chen
Ke-Si Shi
Yao-Sen Wu
Jun Xuan
Zeng-Ming Zheng
Xi-Bang Chen
Xiang-Yang Wang
Journal: Biomedicine & Pharmacotherapy (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Celastrol; Inflammation; Intervertebral disc degeneration; NF-κB.
Affiliations: Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China., Jinhua Municipal Central Hospital, Jinhua Hospital of Zhejiang University, People's Republic of China., The First Clinical College, Wenzhou Medical University, Wenzhou, 325027, People's Republic of China., Department of Postgraduate Education, Wenzhou Medical University, Wenzhou, 325027, People's Republic of China., Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China. Electronic address: .

Abstract:  Celastrol has been reported to exert therapeutic potential on pro-inflammatory diseases including asthma, Crohn's disease, arthritis and neurodegenerative disorders via inhibiting NF-κB 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-1β 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-1β in nucleus pulposus cells, also phosphorylation of IκBα and p65 were attenuated by celastrol, indicating NF-κB 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-1β 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. 

Retracted: No

PubPeer comments:
 Figure 1 was brought to my attention by a reader. * Red boxes: The 50 nM and 200 nM panels appear to show an overlap. ![file] , 
 An additional finding in Figure 6. * Yellow boxes: the Control and IL+Cel panels appear to show an overlap, albeit shown at different intensities. ![file] , 
 An additional finding in Figure 7. * Green boxes: the Control and Cel panels appear to show an overlap. ![file] , 
 The same reader from comment #1 also found a possible overlap between Figure 3D from this paper and Figure 1A from another paper by the same researchers, i.e. Jian Chen et al, Cell Death Dis 2017; 8: e3090, DOI: 10.1038 cddis.2017.490 - https: pubpeer.com publications 8033017FB51442A57538C251287287 Shown here with red boxes. Note that the panels represent different proteins and experiments. ![file] ,