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Updated: Aug 20, 2025
Inducing Apical Periodontitis in Mice
Published on: August 6, 2019
Macrophage M1 polarization mediated via the IL-6/STAT3 pathway contributes to apical periodontitis induced by
Xuan Chen1, Jinge Dou1, Zhuohui Fu1
1National Clinical Research Center for Oral Diseases & State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Department of Operative Dentistry and Endodontics, Sichuan University, Chengdu, China.
Objective:
To investigate the involvement of IL-6/STAT3 signaling pathway activation in macrophage polarization and bone destruction related to apical periodontitis (AP) stimulated by Porphyromonas gingivalis.
Methodology:
Macrophage polarization, IL-6/STAT3 expression, and the presence of P. gingivalis were detected in human AP tissues via RT-qPCR, western blotting, and immunohistochemistry staining. Murine bone marrow derived macrophages were isolated and cultured with P. gingivalis W83 in vitro, and levels of macrophage IL-6 expression, STAT3 phosphorylation, and macrophage polarization with or without the selective STAT3 phosphorylation inhibitor Stattic (5 μM) were detected via ELISA, western blotting, RT-qPCR, and flow cytometry, respectively. P. gingivalis-induced murine AP models were constructed, and bone destruction and macrophage polarization in the apical region were evaluated. Transwell co-culture systems were used to investigate the effects of macrophages infected with P. gingivalis on osteogenesis and osteoclastogenesis.
Results:
P. gingivalis was detected in human AP tissues that highly expressed IL-6/STAT3, and the M1 subtype of macrophages was more abundant in these tissues. P. gingivalis infection induced IL-6 expression, STAT3 phosphorylation, and M1 polarization of macrophages, while 5 μM of Stattic partially abolished these activation effects. Systemic STAT3 blockade via oral administration of Stattic at a dose of 25 mg kg-1 alleviated murine periapical bone resorption and apical infiltration of M1 macrophages induced by P. gingivalis infection in vivo. Furthermore, macrophages infected with P. gingivalis promoted bone destruction via secretion of IL-6, TNF-α, and RANKL, which hinder pre-osteoblast expression of Runx2 and accelerate pre-osteoclast expression of NFAT2.
Conclusions:
The activation of IL-6/STAT3 signaling pathway is involved in mediating macrophages M1 polarization in the P. gingivalis induced apical inflammatory context and may also be intimately involved in the bone loss caused by P. gingivalis infection, directing the M1 macrophage infiltration during the progression of AP.
Insights
Porphyromonas gingivalis infection activates the IL-6/STAT3 pathway, driving M1 macrophage polarization and bone loss in apical periodontitis. Blocking STAT3 phosphorylation reduces inflammation and bone resorption.
Area of Science:
- Immunology
- Oral Biology
- Pathology
Background:
- Apical periodontitis (AP) is an inflammatory condition often caused by bacterial infection.
- Porphyromonas gingivalis is a key pathogen implicated in AP pathogenesis.
- The IL-6/STAT3 signaling pathway plays a role in inflammatory responses and immune cell function.
Purpose of the Study:
- To investigate the role of the IL-6/STAT3 signaling pathway in macrophage polarization and bone destruction during P. gingivalis-induced apical periodontitis.
- To determine if inhibiting STAT3 phosphorylation can mitigate AP-associated bone loss.
Main Methods:
- Analysis of human AP tissues for P. gingivalis, IL-6/STAT3 expression, and macrophage polarization.
- In vitro studies using murine macrophages stimulated with P. gingivalis and treated with a STAT3 inhibitor (Stattic).
- In vivo studies using a murine AP model treated with Stattic to assess bone resorption and macrophage infiltration.
Main Results:
- Human AP tissues showed high IL-6/STAT3 expression and abundant M1 macrophages, with presence of P. gingivalis.
- P. gingivalis infection induced M1 polarization and IL-6/STAT3 activation in vitro, which was partially inhibited by Stattic.
- In vivo, Stattic treatment reduced periapical bone resorption and M1 macrophage infiltration.
- P. gingivalis-infected macrophages promoted bone destruction by secreting inflammatory mediators.
Conclusions:
- IL-6/STAT3 pathway activation is crucial for M1 macrophage polarization in P. gingivalis-induced AP.
- This pathway is implicated in P. gingivalis-driven bone loss by directing M1 macrophage infiltration.
- Targeting STAT3 phosphorylation may offer a therapeutic strategy for apical periodontitis.
