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. 2025 May;52(5):773-786.
doi: 10.1111/jcpe.14144. Epub 2025 Feb 20.

Hyperuricemia Exacerbates Experimental Periodontitis via Uric Acid-Induced Periodontal Inflammation and Oxidative Stress

Zhicong Wu  1 , Li Zhao  2 , Yi Guo  1   3 , Chuyin Lin  1 , Peipei Lu  1 , Qian He  1 , Yinghong Zhou  4 , Xinhong Wang  1 , Ting Yu  1
Affiliations

Hyperuricemia Exacerbates Experimental Periodontitis via Uric Acid-Induced Periodontal Inflammation and Oxidative Stress

Zhicong Wu et al. J Clin Periodontol. 2025 May.

Abstract

Aim: To investigate the effects of hyperuricemia on periodontitis and the underlying mechanisms by establishing combined animal and cell models.

Methods: A hyperuricemia mouse model was established by potassium oxonate injection, with sodium carboxymethylcellulose treatment serving as controls. Both models were treated with or without periodontitis induction (n = 10/group). RAW264.7 macrophages and THP-1-derived macrophages were stimulated with Porphyromonas gingivalis -lipopolysaccharide in the presence of normal or excessive concentrations of uric acid. Allopurinol intervention was applied to both animal and cell models. Periodontal destruction was measured by micro-computed tomography and histology. The immune response and oxidative stress in the periodontium and macrophages were assessed using various methods including immunohistochemistry, quantitative PCR, western blotting, flow cytometry and multiplex cytokine assays.

Results: Potassium oxonate successfully induced hyperuricemia without affecting serum glucose/lipid levels or xanthine oxidoreductase activity. In mice with periodontitis, hyperuricemia exacerbated alveolar bone loss and the presence of osteoclasts and M1 macrophages. Mechanistically, hyperuricemia promoted NLRP3 inflammasome activation, disrupted the inflammatory cytokine response and exacerbated oxidative stress both in the periodontium and in vitro. Allopurinol treatment reversed all relevant changes in both mice and macrophages.

Conclusion: Hyperuricemia exacerbates periodontitis possibly via uric acid-induced periodontal inflammation and oxidative stress.

Keywords: hyperuricemia; oxidative stress; periodontal diseases; potassium oxonate; purine; uric acid.

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References

    1. Andrade‐Oliveira, V., O. Foresto‐Neto, I. Watanabe, R. Zatz, and N. Camara. 2019. “Inflammation in Renal Diseases: New and Old Players.” Frontiers in Pharmacology 10: 1192.
    1. Battelli, M. G., M. Bortolotti, L. Polito, and A. Bolognesi. 2018. “The Role of Xanthine Oxidoreductase and Uric Acid in Metabolic Syndrome.” Biochimica et Biophysica Acta ‐ Molecular Basis of Disease 1864: 2557–2565.
    1. Botelho, J., V. Machado, Y. Leira, L. Proenca, L. Chambrone, and J. J. Mendes. 2022. “Economic Burden of Periodontitis in the United States and Europe: An Updated Estimation.” Journal of Periodontology 93: 373–379.
    1. Butler, F., A. Alghubayshi, and Y. Roman. 2021. “The Epidemiology and Genetics of Hyperuricemia and Gout Across Major Racial Groups: A Literature Review and Population Genetics Secondary Database Analysis.” Journal of Personalized Medicine 11: 231.
    1. Chauhan, K., P. Pattharanitima, F. Piani, et al. 2022. “Prevalence and Outcomes Associated With Hyperuricemia in Hospitalized Patients With COVID‐19.” American Journal of Nephrology 53: 78–86.

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