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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Article info
Publication history
Accepted:
January 12,
2023
Received in revised form:
January 4,
2023
Received:
July 6,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
