Frontiers in Cell and Developmental Biology (Nov 2020)
RNA-Binding Protein HuR Suppresses Inflammation and Promotes Extracellular Matrix Homeostasis via NKRF in Intervertebral Disc Degeneration
- Zhenxuan Shao,
- Zhenxuan Shao,
- Zhenxuan Shao,
- Zhuolong Tu,
- Yifeng Shi,
- Yifeng Shi,
- Yifeng Shi,
- Sunlong Li,
- Sunlong Li,
- Sunlong Li,
- Aimin Wu,
- Aimin Wu,
- Aimin Wu,
- Yaosen Wu,
- Yaosen Wu,
- Yaosen Wu,
- Naifeng Tian,
- Naifeng Tian,
- Naifeng Tian,
- Liaojun Sun,
- Liaojun Sun,
- Liaojun Sun,
- Zongyou Pan,
- Linwei Chen,
- Weiyang Gao,
- Weiyang Gao,
- Weiyang Gao,
- Yifei Zhou,
- Yifei Zhou,
- Yifei Zhou,
- Xiangyang Wang,
- Xiangyang Wang,
- Xiangyang Wang,
- Xiaolei Zhang,
- Xiaolei Zhang,
- Xiaolei Zhang,
- Xiaolei Zhang
Affiliations
- Zhenxuan Shao
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Zhenxuan Shao
- Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China
- Zhenxuan Shao
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Zhuolong Tu
- Department of Burn, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Yifeng Shi
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Yifeng Shi
- Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China
- Yifeng Shi
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Sunlong Li
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Sunlong Li
- Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China
- Sunlong Li
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Aimin Wu
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Aimin Wu
- Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China
- Aimin Wu
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Yaosen Wu
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Yaosen Wu
- Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China
- Yaosen Wu
- 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
- Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China
- Naifeng Tian
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Liaojun Sun
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Liaojun Sun
- Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China
- Liaojun Sun
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Zongyou Pan
- Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
- Linwei Chen
- Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
- Weiyang Gao
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Weiyang Gao
- Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China
- Weiyang Gao
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Yifei Zhou
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Yifei Zhou
- Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China
- Yifei Zhou
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Xiangyang Wang
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
- Xiangyang Wang
- Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China
- Xiangyang Wang
- 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
- Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China
- Xiaolei Zhang
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China
- Xiaolei Zhang
- Chinese Orthopedic Regenerative Medicine Society, Hangzhou, China
- DOI
- https://doi.org/10.3389/fcell.2020.611234
- Journal volume & issue
-
Vol. 8
Abstract
Intervertebral disc degeneration (IVDD) has been reported to be a major cause of low back pain. Studies have demonstrated that IVDD may be dysregulated at the transcriptional level; however, whether post-transcriptional regulation is involved is still unknown. The current study aimed to illustrate the role of Human antigen R (HuR), an RNA binding protein involved in post-transcriptional regulation, in IVDD. The results showed that the expression of HuR was decreased in degenerative nucleus pulposus (NP) tissues as well as in TNF-α-treated NP cells. Downregulation of HuR may lead to increased inflammation and extracellular matrix (ECM) degradation in TNF-α-treated NP cells; however, these effects were not reversed in HuR overexpressed NP cells. Inhibition of the NF-κB signaling pathway attenuates inflammation and ECM degradation in HuR-deficient NP cells. A mechanism study showed that HuR prompted NKRF mRNA stability via binding to its AU-rich elements, and upregulation of NKRF suppressed inflammation and ECM degradation in HuR-deficient NP cells. Furthermore, we found that NKRF, but not HuR, overexpression ameliorated the process of IVDD in rats in vivo. In conclusion, HuR suppressed inflammation and ECM degradation in NP cells via stabilizing NKRF and inhibiting the NF-κB signaling pathway; NKRF, but not HuR, may serve as a potential therapeutic target for IVDD.
Keywords