Frontiers in Pharmacology (Aug 2019)
Luteoloside Inhibits IL-1β-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration
- Jialiang Lin,
- Jialiang Lin,
- Jialiang Lin,
- Jiaoxiang Chen,
- Jiaoxiang Chen,
- Jiaoxiang Chen,
- Zengjie Zhang,
- Zengjie Zhang,
- Zengjie Zhang,
- Tianzhen Xu,
- Tianzhen Xu,
- Tianzhen Xu,
- Tianzhen Xu,
- Zhenxuan Shao,
- Zhenxuan Shao,
- Zhenxuan Shao,
- Xiaobin Wang,
- Xiaobin Wang,
- Xiaobin Wang,
- Yuanzhe Ding,
- Yuanzhe Ding,
- Yuanzhe Ding,
- Naifeng Tian,
- Naifeng Tian,
- Naifeng Tian,
- Haiming Jin,
- Haiming Jin,
- Haiming Jin,
- Sunren Sheng,
- Sunren Sheng,
- Sunren Sheng,
- Weiyang Gao,
- Weiyang Gao,
- Weiyang Gao,
- Yan Lin,
- Yan Lin,
- Yan Lin,
- Xiaolei Zhang,
- Xiaolei Zhang,
- Xiaolei Zhang,
- Xiaolei Zhang,
- Xiangyang Wang,
- Xiangyang Wang,
- Xiangyang Wang,
- Xiangyang Wang
Affiliations
- Jialiang Lin
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Jialiang Lin
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Jialiang Lin
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Jiaoxiang Chen
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Jiaoxiang Chen
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Jiaoxiang Chen
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Zengjie Zhang
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Zengjie Zhang
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Zengjie Zhang
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Tianzhen Xu
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Tianzhen Xu
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Tianzhen Xu
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Tianzhen Xu
- Department of Orthopaedics, The Third Affiliated Hospital and Ruian People’s Hospital of Wenzhou Medical University, Ruian, China
- Zhenxuan Shao
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Zhenxuan Shao
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Zhenxuan Shao
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Xiaobin Wang
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Xiaobin Wang
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Xiaobin Wang
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Yuanzhe Ding
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Yuanzhe Ding
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Yuanzhe Ding
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Naifeng Tian
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Naifeng Tian
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Naifeng Tian
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Haiming Jin
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Haiming Jin
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Haiming Jin
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Sunren Sheng
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Sunren Sheng
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Sunren Sheng
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Weiyang Gao
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Weiyang Gao
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Weiyang Gao
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Yan Lin
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Yan Lin
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Yan Lin
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Xiaolei Zhang
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Xiaolei Zhang
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Xiaolei Zhang
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Xiaolei Zhang
- Chinese Orthopaedic Regenerative Medicine Society, Hangzhou, China
- Xiangyang Wang
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Xiangyang Wang
- Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China
- Xiangyang Wang
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Xiangyang Wang
- Chinese Orthopaedic Regenerative Medicine Society, Hangzhou, China
- DOI
- https://doi.org/10.3389/fphar.2019.00868
- Journal volume & issue
-
Vol. 10
Abstract
Intervertebral disk degeneration (IDD) is the major cause of low back pain (LBP), which affects 80% of the world’s population. Interleukin 1 beta (IL-1β) is a major inflammatory factor that accelerates disk degeneration, and IL-1β levels increase in degenerative disks. It has recently been reported that luteoloside—a type of flavonoid glycoside—has anti-inflammatory properties. In the present study, we investigated the protective potential of luteoloside in IDD. We found that luteoloside maintains cell morphology and inhibits apoptosis (indicated by the reduced expression of cleaved caspase 3) in IL-1β-treated nucleus pulposus (NP) cells. It also suppresses inflammatory mediators—nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS)—in IL-1β-treated NP cells. Furthermore, we found increased collagen II and aggrecan expression and reduced MMP13 and ADAMTS5 expression in luteoloside-treated NP cells in the presence of IL-1β. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is involved in apoptosis, inflammation, and extracellular matrix (ECM) homeostasis. Mechanistic studies revealed that the NF-κB signaling pathway is inhibited by luteoloside, and Nrf2 is involved in the regulation of luteoloside in NF-κB signaling because Nrf2 knockdown reduced the suppressive effect of luteoloside on NF-κB signaling. We also established a puncture-induced rat IDD model and demonstrated that the persistent intraperitoneal injection of luteoloside ameliorates the progression of IDD. In conclusion, we demonstrated that luteoloside activates the Nrf2/HO-1 signaling axis and is a potential therapeutic medicine for IDD.
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