Sirtuin 3 deficiency exacerbates age‐related periodontal disease.

Background: Sirtuin 3 (SIRT3), a mitochondrial NAD+‐dependent deacetylase, has received much attention for its effect on metabolism and aging. However, the role of SIRT3 in periodontal disease remains unknown. Objective: This study aimed to investigate the functional role of SIRT3 in age‐related periodontal disease and underlying mechanisms. Methods: Sixteen mice were randomly assigned into four groups: the young wild type (WT), the aged WT, the young SIRT3‐knockout (KO), and the aged SIRT3‐KO. SIRT3 and cyclophilin D (CypD) expression and protein lysine acetylation levels in alveolar bones were detected by western blot. The bone architecture and the distance of CEJ‐ABC were assessed using micro‐CT and HE staining. The osteoclast number was observed through tartrate‐resistant acid phosphatase (TRAP) staining. Mitochondrial morphology in SIRT3 knockdown MC3T3‐E1 osteoblastic cells was analyzed by Immunofluorescence staining. In gingival tissues, the NAD+/NADH ratio was measured, and oxidative stress was detected by MitoSOX staining, HO‐1 staining, and MnSOD expression. Mitochondrial biogenesis was measured by PGC‐1α expression and oxygen consumption rate (OCR). Results: In parallel with the imbalanced NAD+/NADH ratio, the SIRT3 expression was significantly decreased in the alveolar bones of the aged mice, accompanied by a global elevation of protein acetylation levels. The aged SIRT3‐KO group showed the highest rate of bone resorption and the largest number of TRAP‐positive osteoclasts among the four groups. Moreover, the reactive oxygen species level was up‐regulated in the young and the aged SIRT3‐KO groups. SIRT3 deficiency promoted mitochondrial fission and increased the CypD expression. Furthermore, the lack of SIRT3 reduced the PGC‐1α expression in gingival tissues and exhibited a significant reduction in maximal OCR. Conclusion: Reduced SIRT3 abundance contributes to aged‐related periodontal disease via the exacerbation of oxidative stress and mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

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