Abstract
Objectives
Aging is characterized by chronic inflammatory activity. Senescent cells increase with chronic inflammation and age-related pathologies, including periodontal disease. As a critical regulator of tissue inflammaging, we hypothesized that 5α reductase (5αR) is associated with periodontal disease and bacteria-induced senescence in gingival fibroblasts.
Materials and methods
We recruited 36 patients with periodontitis, measured 5αR immunohistochemically before and after periodontal treatment, and compared the expression of 5αR in gingival biopsies from 12 healthy individuals. We then tested the impact of Porphyromonas gingivalis on gingival fibroblasts treated with or without D-galactose-induced cell senescence. We treated primary gingival fibroblasts with D-galactose-supplemented media (0 µM, 50 µM, 100 µM, 1 mM, 10 mM, 50 mM) to induce senescence. The expression of type 1 and type 2 5αR was analyzed with real-time PCR and immunocytochemistry. The levels of IL-6, IL-8, TNF-α, and MCP-1 in fibroblast cultures were evaluated by multiplex immunoassay.
Results
In gingival biopsies from patients with periodontal disease, the expression of 5αR was significantly higher than in samples from individuals without periodontal disease (p < 0.001). Periodontal treatment significantly reduced the expression of 5αR in gingival tissues (p < 0.001) to levels comparable in healthy individuals. Gingival fibroblasts exposed to D-galactose-supplemented media had a dose-dependent and significant increase in 5αR expression (p < 0.001). P. gingivalis caused statistically higher type 1 and type 2 5αR expression in gingival fibroblast cells. This effect was exacerbated by the lower doses of D-galactose (p = 0.037). Cells infected with P. gingivalis produced significantly higher levels of IL-6, IL-8, TNF-α, and MCP-1 (p < 0.05) regardless of the D-galactose exposure.
Conclusion
The results suggested that 5αR plays a role in periodontal disease and mediates the senescence-induced response to P. gingivalis in gingival fibroblasts.
Clinical relevance
Periodontal diseases and aging can increase the production of 5-alpha reductase in the gingival tissue.
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Data availability
The data which obtain from patient supporting this study cannot been made available due to ethical and legal.
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This study was supported by a grant from The Scientific and Technological Research Council of Turkiye (TUBİTAK) (the grant number 2214/A 1059B141600460.)
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All authors contributed to the conception and design of the work. Y.Ö.K., R.O., and A.K. desinged study. The clinical study did by Y.Ö.K. The in vitro experiments were by Y.Ö.K. and A.K; and K.K. analyzed the data. Y.Ö.K., E.B., and A.K. contributed to the preparation of the manuscript. All authors gave their final approval and agreed to be accountable for all aspects of the work.
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All procedure performed in study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from all participants included in the study. This study was approved by Institutional Ethics Committee of the Ataturk University, Faculty of Dentistry. (approval no. 7–02/2016, 02/10/2016).
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Özkan Karasu, Y., Orbak, R., Kaşalı, K. et al. Porphyromonas gingivalis enhances the senescence-induced increase of 5-alpha reductase in gingival fibroblasts. Clin Oral Invest 27, 5977–5989 (2023). https://doi.org/10.1007/s00784-023-05211-y
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DOI: https://doi.org/10.1007/s00784-023-05211-y