Sinapic Acid Inhibits IL-1β-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration
Jin-Feng Huang,1,2 Xuan-Qi Zheng,1,2 Jia-Liang Lin,3 Kai Zhang,4 Hai-Jun Tian,4 Wen-Xian Zhou,1,2 Hui Wang,1,2 Ze Gao,5 Hai-Ming Jin,1,2,* Ai-Min Wu1,2,* 1Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Peopl...
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Dove Medical Press
2020-11-01
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author | Huang JF Zheng XQ Lin JL Zhang K Tian HJ Zhou WX Wang H Gao Z Jin HM Wu AM |
author_facet | Huang JF Zheng XQ Lin JL Zhang K Tian HJ Zhou WX Wang H Gao Z Jin HM Wu AM |
author_sort | Huang JF |
collection | DOAJ |
description | Jin-Feng Huang,1,2 Xuan-Qi Zheng,1,2 Jia-Liang Lin,3 Kai Zhang,4 Hai-Jun Tian,4 Wen-Xian Zhou,1,2 Hui Wang,1,2 Ze Gao,5 Hai-Ming Jin,1,2,* Ai-Min Wu1,2,* 1Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2The Second School of Medicine, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Orthopaedics, Peking University Third Hospital, Beijing, People’s Republic of China; 4Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai, People’s Republic of China; 5Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ai-Min Wu; Hai-Ming JinDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109# Xueyuan Road, Wenzhou, Zhejiang 325027, People’s Republic of ChinaTel +86 0577 88002814Fax +86 057788002823Email aiminwu@wmu.edu.cn; kkjinhaiming@126.comBackground: Low back pain (LBP) is a very common condition and leads to serious pain, disability, and price tag all over the world. Intervertebral disk degeneration (IDD) is one of the major reasons that contributed to LBP. The levels of interleukin 1 beta (IL-1β) increase significantly in degenerative disks. IL-1β also accelerates IDD. Sinapic acid (SA) has the effect of anti‐inflammatory, antioxidant and antimicrobial. However, the effect of SA on IDD has never been studied. Therefore, the aim of this study was to figure out whether SA has protective effect on nucleus pulposus (NP) cells and further explore the possible underlying mechanism.Methods: The nucleus pulposus (NP) tissues of rats were collected and cultured into NP cells. The NP cells were stimulated by IL-1β and treated with SA. In vitro treatment effects were evaluated by ELISA, Western blot assay, immunofluorescence, TUNEL method and real-time PCR. We conducted percutaneous needle puncture in the rat tail to build intervertebral disk degeneration model and treated rats with SA. In vivo treatment effects were evaluated by hematoxylin and eosin (HE) and safranin O (SO) staining and magnetic resonance imaging (MRI) method.Results: Our results showed that SA not only inhibited apoptosis but also suppressed inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS) interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in IL-1β-stimulated NP cells. As to extracellular matrix (ECM), SA could increase collagen II and aggrecan levels and reduce the expression of MMP13 and ADAMTS5 during the stimulation of IL-1β. Furthermore, SA could activate nuclear factor‐erythroid 2‐related factor‐2 (Nrf2) to inhibit nuclear factor κB (NF‐κB) induced by IL‐1β. Nrf2 knockdown partly reduced the protective effect of SA on NP cells. Correspondingly, SA ameliorated IDD by promoting Nrf2 expression. In vivo results also showed that SA could delay the progression of IDD.Conclusion: In conclusion, we demonstrated that SA could protect the degeneration of NP cells and revealed the underlying mechanism of SA on Nrf2 activation in NP cells.Keywords: intervertebral disk degeneration, sinapic acid, apoptosis, Nrf2, inflammation |
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language | English |
last_indexed | 2024-12-18T04:03:41Z |
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spelling | doaj.art-ffcf26de143140049d59f162bd4875602022-12-21T21:21:39ZengDove Medical PressJournal of Inflammation Research1178-70312020-11-01Volume 1388389559091Sinapic Acid Inhibits IL-1β-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk DegenerationHuang JFZheng XQLin JLZhang KTian HJZhou WXWang HGao ZJin HMWu AMJin-Feng Huang,1,2 Xuan-Qi Zheng,1,2 Jia-Liang Lin,3 Kai Zhang,4 Hai-Jun Tian,4 Wen-Xian Zhou,1,2 Hui Wang,1,2 Ze Gao,5 Hai-Ming Jin,1,2,* Ai-Min Wu1,2,* 1Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2The Second School of Medicine, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Orthopaedics, Peking University Third Hospital, Beijing, People’s Republic of China; 4Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai, People’s Republic of China; 5Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ai-Min Wu; Hai-Ming JinDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109# Xueyuan Road, Wenzhou, Zhejiang 325027, People’s Republic of ChinaTel +86 0577 88002814Fax +86 057788002823Email aiminwu@wmu.edu.cn; kkjinhaiming@126.comBackground: Low back pain (LBP) is a very common condition and leads to serious pain, disability, and price tag all over the world. Intervertebral disk degeneration (IDD) is one of the major reasons that contributed to LBP. The levels of interleukin 1 beta (IL-1β) increase significantly in degenerative disks. IL-1β also accelerates IDD. Sinapic acid (SA) has the effect of anti‐inflammatory, antioxidant and antimicrobial. However, the effect of SA on IDD has never been studied. Therefore, the aim of this study was to figure out whether SA has protective effect on nucleus pulposus (NP) cells and further explore the possible underlying mechanism.Methods: The nucleus pulposus (NP) tissues of rats were collected and cultured into NP cells. The NP cells were stimulated by IL-1β and treated with SA. In vitro treatment effects were evaluated by ELISA, Western blot assay, immunofluorescence, TUNEL method and real-time PCR. We conducted percutaneous needle puncture in the rat tail to build intervertebral disk degeneration model and treated rats with SA. In vivo treatment effects were evaluated by hematoxylin and eosin (HE) and safranin O (SO) staining and magnetic resonance imaging (MRI) method.Results: Our results showed that SA not only inhibited apoptosis but also suppressed inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS) interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in IL-1β-stimulated NP cells. As to extracellular matrix (ECM), SA could increase collagen II and aggrecan levels and reduce the expression of MMP13 and ADAMTS5 during the stimulation of IL-1β. Furthermore, SA could activate nuclear factor‐erythroid 2‐related factor‐2 (Nrf2) to inhibit nuclear factor κB (NF‐κB) induced by IL‐1β. Nrf2 knockdown partly reduced the protective effect of SA on NP cells. Correspondingly, SA ameliorated IDD by promoting Nrf2 expression. In vivo results also showed that SA could delay the progression of IDD.Conclusion: In conclusion, we demonstrated that SA could protect the degeneration of NP cells and revealed the underlying mechanism of SA on Nrf2 activation in NP cells.Keywords: intervertebral disk degeneration, sinapic acid, apoptosis, Nrf2, inflammationhttps://www.dovepress.com/sinapic-acid-inhibits-il-1beta-induced-apoptosis-and-catabolism-in-nuc-peer-reviewed-article-JIRintervertebral disk degenerationsinapic acidapoptosisnrf2inflammation |
spellingShingle | Huang JF Zheng XQ Lin JL Zhang K Tian HJ Zhou WX Wang H Gao Z Jin HM Wu AM Sinapic Acid Inhibits IL-1β-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration Journal of Inflammation Research intervertebral disk degeneration sinapic acid apoptosis nrf2 inflammation |
title | Sinapic Acid Inhibits IL-1β-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration |
title_full | Sinapic Acid Inhibits IL-1β-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration |
title_fullStr | Sinapic Acid Inhibits IL-1β-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration |
title_full_unstemmed | Sinapic Acid Inhibits IL-1β-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration |
title_short | Sinapic Acid Inhibits IL-1β-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration |
title_sort | sinapic acid inhibits il 1 beta induced apoptosis and catabolism in nucleus pulposus cells and ameliorates intervertebral disk degeneration |
topic | intervertebral disk degeneration sinapic acid apoptosis nrf2 inflammation |
url | https://www.dovepress.com/sinapic-acid-inhibits-il-1beta-induced-apoptosis-and-catabolism-in-nuc-peer-reviewed-article-JIR |
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