Oxidative stress causes alveolar bone loss in metabolic syndrome model mice with type 2 diabetes
Version of Record online: 7 OCT 2008
© 2008 The Authors. Journal compilation © 2008 Blackwell Munksgaard
Journal of Periodontal Research
Volume 44, Issue 1, pages 43–51, February 2009
How to Cite
Ohnishi, T., Bandow, K., Kakimoto, K., Machigashira, M., Matsuyama, T. and Matsuguchi, T. (2009), Oxidative stress causes alveolar bone loss in metabolic syndrome model mice with type 2 diabetes. Journal of Periodontal Research, 44: 43–51. doi: 10.1111/j.1600-0765.2007.01060.x
- Issue online: 7 JAN 2009
- Version of Record online: 7 OCT 2008
- Accepted for publication October 16, 2007
- metabolic syndrome;
- endothelial nitric oxide synthase;
- reactive oxygen species
Background and Objective: Alveolar bone loss is caused by a host response to periodontal pathogens, and its progression is often enhanced by systemic conditions such as insulin resistance.Alveolar bone dehiscence has been observed in KK-Ay mice, which are metabolic syndrome model mice with type 2 diabetes. The aim of this study was to investigate inducements responsible for alveolar bone dehiscence in the KK-Ay mice.
Material and Methods: The expression of endothelial nitric oxide synthase in the mandibles of mice was detected using immunohistochemical staining and the reverse transcription–polymerase chain reaction. After administration of N-acetylcysteine, an antioxidant, to KK-Ay mice, alveolar bone loss and the expression of endothelial nitric oxide synthase protein in gingival keratinocytes and of hydrogen peroxide concentrations in plasma, were analyzed. The effect of hydrogen peroxide on endothelial nitric oxide synthase expression in keratinocytes was examined using cultured keratinocytes.
Results: The expression of endothelial nitric oxide synthase was decreased in gingival keratinocytes from KK-Ay mice compared with gingival keratinocytes from control mice. Administration of N-acetylcysteine to the mice restored endothelial nitric oxide synthase expression in the gingival keratinocytes, suppressed the alveolar bone loss and decreased the hydrogen peroxide concentrations in plasma without the improvement of obesity or diabetes. In vitro, stimulation with hydrogen peroxide decreased the expression level of endothelial nitric oxide synthase in cultured keratinocytes, which was restored by the addition of N-acetylcysteine.
Conclusion: Reactive oxygen species, such as hydrogen peroxide, are responsible for the alveolar bone loss accompanied by decreased endothelial nitric oxide synthase expression in KK-Ay mice. Therefore, we propose a working hypothesis that the generation of oxidative stress is an underlying systemic condition that enhances alveolar bone loss in periodontitis occurring as a complication of diabetes.