Role of ferroptosis in periodontitis: An animal study in rats
- PMID: 37477155
- DOI: 10.1111/jre.13165
Role of ferroptosis in periodontitis: An animal study in rats
Abstract
Objective: This study aimed to investigate (1) the temporal pattern of ferroptosis, an iron-dependent cell death, in ligation-induced rat periodontitis and (2) the effect of ferrostatin-1, a ferroptosis inhibitor, on the model.
Background: Ferroptosis may contribute to various diseases. However, the role of ferroptosis in periodontitis is still fully understood.
Methods: In the first experiment, 25 rats with ligation-induced periodontitis were sacrificed on days 0, 1, 2, 7, and 10. Gingivae were obtained to determine tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and ferroptotic biomarkers, including solute carrier family 3 member 2 (SLC3A2) and solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (Gpx4), via immunoblotting. Using microcomputed tomography (μCT) and histology, the periodontal soft and hard tissue lesions, including dental alveolar bone crest level, bony characteristics of the surrounding alveolus, periodontal tissue inflammation, and periodontal tissue losses, were evaluated. In study two, 16 rats with induced periodontitis were grouped according to ferrostatin-1 treatment. The rats were intraperitoneally injected with solvent or ferrostatin-1 (1.5 mg/kg/day) 1 day before ligation and sacrificed on days 7 and 10. Gingival protein changes and periodontal tissue damage were also examined.
Results: In study one, SLC3A2/SLC7A11 and Gpx4 decreased since day 1; however, TNF-α/IL-1β increased on days 7 and 10. Moreover, the μCT/histology revealed resorptive bony characteristics, inflamed gingival tissue, and periodontal attachment loss. In study two, ferrostatin-1-injected rats exhibited significantly increased SLC3A2/SLC7A11 and Gpx4 but decreased TNF-α/IL-1β than vehicle rats. They also revealed lessened bone resorption, tissue inflammation, and attachment loss.
Conclusion: This study highlights the role of ferroptosis, via the system Xc/Gpx4 pathway, in experimental periodontitis and may serve as a regulatory strategy.
Keywords: bone resorption; ferroptosis; inflammation; periodontium.
© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Similar articles
-
Resveratrol Alleviates Diabetic Periodontitis-Induced Alveolar Osteocyte Ferroptosis Possibly via Regulation of SLC7A11/GPX4.Nutrients. 2023 Apr 28;15(9):2115. doi: 10.3390/nu15092115. Nutrients. 2023. PMID: 37432277 Free PMC article.
-
Jing-Fang n-butanol extract and its isolated JFNE-C inhibit ferroptosis and inflammation in LPS induced RAW264.7 macrophages via STAT3/p53/SLC7A11 signaling pathway.J Ethnopharmacol. 2023 Nov 15;316:116689. doi: 10.1016/j.jep.2023.116689. Epub 2023 Jun 12. J Ethnopharmacol. 2023. PMID: 37315642
-
Lipid Peroxidation and Iron Metabolism: Two Corner Stones in the Homeostasis Control of Ferroptosis.Int J Mol Sci. 2022 Dec 27;24(1):449. doi: 10.3390/ijms24010449. Int J Mol Sci. 2022. PMID: 36613888 Free PMC article. Review.
-
Astragaloside IV regulates the ferroptosis signaling pathway via the Nrf2/SLC7A11/GPX4 axis to inhibit PM2.5-mediated lung injury in mice.Int Immunopharmacol. 2022 Nov;112:109186. doi: 10.1016/j.intimp.2022.109186. Epub 2022 Sep 15. Int Immunopharmacol. 2022. PMID: 36115280 Review.
-
Characterization of ligature-induced experimental periodontitis.Microsc Res Tech. 2018 Dec;81(12):1412-1421. doi: 10.1002/jemt.23101. Epub 2018 Oct 23. Microsc Res Tech. 2018. PMID: 30351474
Cited by
-
A multi-platform analysis of human gingival crevicular fluid reveals ferroptosis as a relevant regulated cell death mechanism during the clinical progression of periodontitis.Int J Oral Sci. 2024 May 27;16(1):43. doi: 10.1038/s41368-024-00306-y. Int J Oral Sci. 2024. PMID: 38802345 Free PMC article.
-
Unraveling ferroptosis in osteogenic lineages: implications for dysregulated bone remodeling during periodontitis progression.Cell Death Discov. 2024 Apr 26;10(1):195. doi: 10.1038/s41420-024-01969-6. Cell Death Discov. 2024. PMID: 38670955 Free PMC article.
References
REFERENCES
-
- Lou J, Zhou Y, Feng Z, et al. Caspase-independent regulated necrosis pathways as potential targets in cancer management. Front Oncol. 2020;10:616952.
-
- Hassannia B, Vandenabeele P, Vanden BT. Targeting ferroptosis to iron out cancer. Cancer Cell. 2019;35(6):830-849.
-
- Qi J, Kim JW, Zhou Z, Lim CW, Kim B. Ferroptosis affects the progression of nonalcoholic steatohepatitis via the modulation of lipid peroxidation-mediated cell death in mice. Am J Pathol. 2020;190(1):68-81.
-
- Tang D, Chen X, Kang R, Kroemer G. Ferroptosis: molecular mechanisms and health implications. Cell Res. 2021;31(2):107-125.
-
- Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol. 2021;22(4):266-282.
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources