Abstract
Periodontitis, characterized by progressive alveolar bone destruction, leads to the loss of attachment and stability of the affected teeth. Macrophages, especially the proinflammatory M1 subtype, are key in periodontitis pathogenesis, driving the disease's inflammatory and destructive processes. Despite existing insight into their involvement, comprehensive understanding of the underlying molecular mechanisms remains limited. TRPV1 is a non-selective cation channel protein and is known to regulate cellular function and homeostasis in macrophages. Our research objective was to investigate the impact of TRPV1 on the proinflammatory attributes of M1 macrophages in periodontal tissues, exploring potential mechanistic pathways. A mouse model of periodontitis was established using Porphyromonas gingivalis inoculation and ligature application around the maxillary second molar. Immunohistological analysis showed a significant reduction in macrophage TRPV1 expression in periodontitis-induced mice. Treatment with capsaicin, a TRPV1 agonist, was observed to effectively elevate TRPV1 expression in these macrophages. Furthermore, micro-computed tomography analysis revealed a marked decrease in alveolar bone resorption in the capsaicin -treated group, compared with vehicle and healthy control groups. Our in vitro findings show that capsaicin treatment successfully attenuated LPS-induced TNF-α and IL-6 production in macrophages, mediated through NRF2 activation, consequently reducing intracellular ROS levels. These findings suggest that TRPV1 agonists, through modulating M1 macrophage activity and up-regulating TRPV1, could be a novel therapeutic approach in periodontal disease management.
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Data Availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- H&E:
-
Haematoxylin/eosin
- TRAP:
-
Tartrate-resistant acid phosphatase
- CAP:
-
Capsaicin
- TRPV1:
-
Transient receptor potential vanilloid type1
- LPS:
-
Lipopolysaccharide;
- TNF-α:
-
Tumor necrosis factor-α
- IL-6:
-
Interleukin-6
- qRT-PCR:
-
Quantitative real-time polymerase chain reaction
- ROS:
-
Reactive Oxygen Species
- IFN-γ:
-
Interferon-γ;
- ANOVA:
-
One-way analysis of variance
- Micro-CT:
-
Micro–Computed Tomography
- 3D:
-
Three dimensional
- CEJ:
-
Cemento-enamel junction
- ABC:
-
Alveolar bone crest
- P. gingivalis :
-
Porphyromonas gingivalis
- DAPI, 4’:
-
6-Diamidino-2-phenylindole;
- NRF2:
-
Nuclear factor erythroid 2-related factor 2
- HO-1:
-
Heme oxygenase-1
- RANKL:
-
Receptor activator of nuclear factor-κB ligand
- Keap1:
-
Kelch-like ECH-associated protein 1
- SD:
-
Standard deviation
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Funding
This work was supported by National Science Foundation of China (Grant No. 82170939, 82100995), International Cooperation Project of Science and Technology in Guangdong Province (Grant No. 2023A0505050158), Guangdong Basic and Applied Basic Research Foundation (Grant No. 2023A1515010327), Natural Science Foundation of Guangdong Province (Grant No. 2023A1515012257), Science and Technology Projects in Guangzhou (Grant No. SL2023A04J01702), Natural Science Foundation of Guangdong Province (Grant No. 2021A1515010876).
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Yiyang Li contributed to conception, design, data acquisition, analysis, interpretation, drafted and critically revised the manuscript; Lingling Chen, Zhengmei Lin contributed to conception, design, interpretation and critically revised the manuscript; Xiaotong Guo, Peimeng Zhan, Shuheng Huang, Jiayao Chen contributed to data acquisition, analysis and interpretation; Yujie Zhou, Wentao Jiang contributed to design and data acquisition. All authors gave final approval and agree to be accountable for all aspects of the work.
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10753_2024_2024_MOESM1_ESM.tif
Supplementary file1 Fig. 1 The toxic effect of capsaicin on macrophages in 24 h conducted by cell counting Kit-8. ***p < 0.001; ****p < 0.0001; ns, no significant. Data represents mean ± SD performed in triplicate. (TIF 209 KB)
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Li, Y., Guo, X., Zhan, P. et al. TRPV1 Regulates Proinflammatory Properties of M1 Macrophages in Periodontitis Via NRF2. Inflammation (2024). https://doi.org/10.1007/s10753-024-02024-3
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DOI: https://doi.org/10.1007/s10753-024-02024-3