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IL-37 alleviates intervertebral disc degeneration via the IL-1R8/NF-κB pathway

  • Author Footnotes
    a These authors have contributed equally to this work.
    Sunlong Li
    Footnotes
    a These authors have contributed equally to this work.
    Affiliations
    Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China

    The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
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  • Author Footnotes
    a These authors have contributed equally to this work.
    Xiangxiang Pan
    Footnotes
    a These authors have contributed equally to this work.
    Affiliations
    Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China

    The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
    Search for articles by this author
  • Author Footnotes
    a These authors have contributed equally to this work.
    Yuhao Wu
    Footnotes
    a These authors have contributed equally to this work.
    Affiliations
    Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China

    The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
    Search for articles by this author
  • Yiting Tu
    Affiliations
    Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China

    The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
    Search for articles by this author
  • Weijun Hong
    Affiliations
    Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China

    The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
    Search for articles by this author
  • Jiaping Ren
    Affiliations
    Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China

    The First School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
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  • Jiansen Miao
    Affiliations
    Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China

    The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
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  • Tengjie Wang
    Affiliations
    Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China

    The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
    Search for articles by this author
  • Weiyi Xia
    Affiliations
    Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China

    The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
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  • Jiajie Lu
    Affiliations
    Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China

    The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
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  • Jiaoxiang Chen
    Affiliations
    Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China

    The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
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  • Xuqi Hu
    Affiliations
    Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang Province, China
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  • Yan Lin
    Correspondence
    Corresponding author. Yan Lin. (Yan Lin).
    Affiliations
    Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China

    The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
    Search for articles by this author
  • Xiaolei Zhang
    Correspondence
    Corresponding author. Xiaolei Zhang. (Xiaolei Zhang).
    Affiliations
    Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China

    The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
    Search for articles by this author
  • Xiangyang Wang
    Correspondence
    Corresponding author. Xiangyang Wang, Address: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 West Xueyuan Road, Wenzhou, Zhejiang Province, 325027, China. Tel.: +86 577- 0577-86680500; fax: +86 577- 0577-86680500 (Xiangyang Wang).
    Affiliations
    Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China

    The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
    Search for articles by this author
  • Author Footnotes
    a These authors have contributed equally to this work.
Published:January 20, 2023DOI:https://doi.org/10.1016/j.joca.2023.01.006

      Summary

      Objective

      Intervertebral disc degeneration (IDD) has been reported to be a major cause of low back pain. Interleukin (IL)-37 is an anti-inflammatory cytokine of the interleukin-1 family, which exerts salutary physiological effects. In this study, we assessed the protective effect of IL-37 on IDD progression and its underlying mechanisms.

      Methods

      Immunofluorescence (IF) was conducted to measure IL-37 expression in nucleus pulposus tissues. CCK-8 assay and Edu staining were used to examine the vitality of IL-37 treated nucleus pulposus cells (NPCs). Western blot, qPCR, ELISA as well as immunohistochemistry were used to assess senescence associated secreted phenotype (SASP) factors expression; and NF-κB pathway was evaluated by western blot and IF; while IL-1R8 knock-down by siRNAs was performed to ascertain its significance in the senescence phenotype modulated by IL-37. The therapeutic effect of IL-37 on IDD were evaluated in puncture-induced rat model using X-ray, Hematoxylin-Eosin, Safranin O-Fast Green, and alcian blue staining.

      Results

      We found IL-37 expression decreased in the IDD process. In virto, IL-37 suppressed SASP factors level and senescence phenotype in IL-1β treated NPCs. In vivo, IL-37 alleviated the IDD progression in the puncture-induced rat model. Mechanistic studies demonstrated that IL-37 inhibited IDD progression by downregulating NF-κB pathway activation in NPCs by activating IL-1R8.

      Conclusion

      The present study suggests that IL-37 delays the IDD development through the IL-1R8/NF-κB pathway, which suggests IL-37 as a promising novel target for IDD therapy.

      Keywords

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