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Celastrol reduces IL-1β induced matrix catabolism, oxidative stress and inflammation in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration in vivo.
Biomed Pharmacother. 2017 Jul; 91:208-219.BP

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.

Authors+Show 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.Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 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.Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 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.Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 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.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: callmeroger@126.com.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: xiangyangwang2016@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28458159

Citation

Chen, Jian, et al. "Celastrol Reduces IL-1β Induced Matrix Catabolism, Oxidative Stress and Inflammation in Human Nucleus Pulposus Cells and Attenuates Rat Intervertebral Disc Degeneration in Vivo." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 91, 2017, pp. 208-219.
Chen J, Xuan J, Gu YT, et al. Celastrol reduces IL-1β induced matrix catabolism, oxidative stress and inflammation in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration in vivo. Biomed Pharmacother. 2017;91:208-219.
Chen, J., Xuan, J., Gu, Y. T., Shi, K. S., Xie, J. J., Chen, J. X., Zheng, Z. M., Chen, Y., Chen, X. B., Wu, Y. S., Zhang, X. L., & Wang, X. Y. (2017). Celastrol reduces IL-1β induced matrix catabolism, oxidative stress and inflammation in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration in vivo. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 91, 208-219. https://doi.org/10.1016/j.biopha.2017.04.093
Chen J, et al. Celastrol Reduces IL-1β Induced Matrix Catabolism, Oxidative Stress and Inflammation in Human Nucleus Pulposus Cells and Attenuates Rat Intervertebral Disc Degeneration in Vivo. Biomed Pharmacother. 2017;91:208-219. PubMed PMID: 28458159.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Celastrol reduces IL-1β induced matrix catabolism, oxidative stress and inflammation in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration in vivo. AU - Chen,Jian, AU - Xuan,Jun, AU - Gu,Yun-Tao, AU - Shi,Ke-Si, AU - Xie,Jun-Jun, AU - Chen,Jiao-Xiang, AU - Zheng,Zeng-Ming, AU - Chen,Yu, AU - Chen,Xi-Bang, AU - Wu,Yao-Sen, AU - Zhang,Xiao-Lei, AU - Wang,Xiang-Yang, Y1 - 2017/04/28/ PY - 2017/02/22/received PY - 2017/04/20/revised PY - 2017/04/20/accepted PY - 2017/5/2/pubmed PY - 2018/3/27/medline PY - 2017/5/2/entrez KW - Celastrol KW - Inflammation KW - Intervertebral disc degeneration KW - NF-κB SP - 208 EP - 219 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 91 N2 - 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. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/28458159/Celastrol_reduces_IL_1β_induced_matrix_catabolism_oxidative_stress_and_inflammation_in_human_nucleus_pulposus_cells_and_attenuates_rat_intervertebral_disc_degeneration_in_vivo_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(17)30819-3 DB - PRIME DP - Unbound Medicine ER -