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Updated: Aug 26, 2025
Robust Ligature-Induced Model of Murine Periodontitis for the Evaluation of Oral Neutrophils
Published on: January 21, 2020
IL-1 receptor antagonist (IL-1RA) suppresses a hyper-IL-17 response-mediated bone loss in a murine experimental
Jinmei Zhang1, Angela X Wang2, Yafei Wu3
1Department of Periodontics, College of Dentistry, University of Iowa, Iowa City, IA, USA; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Objective:
We aimed to assess the role of interleukin - 1 receptor antagonist (IL-1RA) in a ligature-induced periodontal (LIP) model and the mechanism of IL-1RA in regulating the IL-17-mediated periodontal bone loss.
Design:
Periodontal bone loss was induced through the LIP model in WT and Il1ra-/- mice and measured by micro(μ) CT. Transcription of upstream IL-17 production signals and downstream targets in the ligated gingiva was compared by the real-time quantitative PCR (RT-qPCR) between WT and Il1ra-/- mice. Single-cell suspensions were prepared in gingiva and cervical lymph nodes and were analyzed by fluorescence-activated cell sorting to quantify IL-17+ cells and IL-17-secreting subpopulations. We locally delivered an anti-IL-17 neutralizing antibody to the ligated gingiva and compared the bone loss with the isotype control antibody-treated Il1ra-/- mice.
Results:
Il1ra-/- mice manifested significantly more bone loss than that of WT mice in the LIP model. Il17 and IL-17-associated transcripts (Il1b, Il6, Il23, Tgfb), Inos, Mrc1, Mmp13, and Rank were upregulated in the gingiva of Il1ra-/- mice in comparison to WT mice. Significantly more IL-17+ immune cells (CD45+IL17+) are present in the gingiva of Il1ra-/- mice with the majority of being TCR γδ T cells (CD45+IL-17+CD3+TCR γδ+) than WT mice. The anti-IL-17 neutralizing antibody treatment attenuated the alveolar bone loss in the LIP model.
Conclusion:
IL-1RA plays a protective role in the murine LIP model by suppressing an expansion of the IL-17+ cells and preventing a hyper-IL-17 response in the gingiva.
