, Volume 41, Issue 5, pp 1852–1863 | Cite as

Progranulin Is Positively Associated with Intervertebral Disc Degeneration by Interaction with IL-10 and IL-17 Through TNF Pathways

  • Shaoyi Wang
  • Jianlu Wei
  • Yuchen Fan
  • Hong Ding
  • Huichao Tian
  • Xiaocong Zhou
  • Lei ChengEmail author


Progranulin (PGRN) is a widely expressed growth factor that effectively inhibits tumor necrosis factor α (TNFα)-mediated inflammatory response. TNFα is involved in intervertebral disc degeneration (IDD) and plays a key role. This study aims to determine the role of PGRN in the intervertebral disc degeneration process. We collected intervertebral discs (IVDs) from humans and mice with different genetic backgrounds. We examined the expression of PGRN in IVD tissues by immunohistochemistry staining and Western blotting assay. We examined the peripheral serum level of PGRN by ELISA assay. Murine IVD tissue samples were taken to undergo safranin O, HE, and immunohistochemistry staining. Primary human nucleus pulposus cells were used for ELISA and RT-PCR assays. PGRN as well as interlukin-10 (IL-10) and interlukin-17 (IL-17) expressions were elevated in degenerative discs and peripheral blood sera. Loss of PGRN led to accelerated disc degeneration in the animal model, along with decreased expression of IL-10 and increased expression of IL-17. Additionally, the PGRN level was positively related to levels of IL-10 and IL-17. In vitro study suggested that PGRN protected against disc degeneration by inducing IL-10 and reducing IL-17. PGRN is associated with intervertebral disc degeneration through interfering with IL-10 and IL-17; thus, PGRN could be an interesting biomarker for diagnosis and a potential treatment target.


progranulin TNFα intervertebral disc degeneration IL-10 IL-17 





intervertebral disk


matrix metallopeptidase 13




tumor necrosis factor α



The study was supported by grants from the National Natural Science Foundation of China (81572191).

Author Contributions

Study concept and design: Lei Cheng and Jianlu Wei.

Raising animals: Shaoyi Wang and Huichao Tian.

Acquisition of data: Shaoyi Wang, Hong Ding and Xiaocong Zhou.

Analysis and interpretation of data: Shaoyi Wang and Jianlu Wei.

Statistical analysis: Shaoyi Wang.

Drafting of the manuscript: Shaoyi Wang, Jianlu Wei, and Yuchen Fan.

Compliance with Ethical Standards

Patients involved in the study provided consent, and the study was approved by medical ethics regulations of the Medical Ethical Committee of Qilu Hospital of Shandong University

Conflict of Interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Shaoyi Wang
    • 1
    • 2
  • Jianlu Wei
    • 1
  • Yuchen Fan
    • 2
  • Hong Ding
    • 1
    • 2
  • Huichao Tian
    • 1
    • 2
  • Xiaocong Zhou
    • 2
  • Lei Cheng
    • 1
    Email author
  1. 1.Department of OrthopaedicsQilu Hospital of Shandong UniversityJinanPeople’s Republic of China
  2. 2.School of MedicineShandong UniversityJinanChina

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