Journal of Inflammation Research (Nov 2020)
Sinapic Acid Inhibits IL-1β-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration
Abstract
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 [email protected]; [email protected]: 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
