Oxidative stress causes alveolar bone loss in metabolic syndrome model mice with type 2 diabetes.
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-A(y) 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-A(y) mice.


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-A(y) 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-A(y) 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.


CONCLUSIONS
Reactive oxygen species, such as hydrogen peroxide, are responsible for the alveolar bone loss accompanied by decreased endothelial nitric oxide synthase expression in KK-A(y) 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.
Ohnishi
T
T
Division of Biochemistry and Molecular Dentistry, Department of Developmental Medicine, Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Bandow
K
K
Kakimoto
K
K
Machigashira
M
M
Matsuyama
T
T
Matsuguchi
T
T
D000111:Acetylcysteine / Q000494:pharmacology; D016301:Alveolar Bone Loss / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000503:physiopathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005881:Gingiva / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D006861:Hydrogen Peroxide / Q000097:blood / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008334:Mandible / Q000201:enzymology; D024821:Metabolic Syndrome / Q000150:complications* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D052250:Nitric Oxide Synthase Type III / Q000032:analysis / Q000187:drug effects; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000494:pharmacology
D000975:Antioxidants; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000111:Acetylcysteine