Sirtuin 3 deficiency exacerbates age-related periodontal disease

Abstract

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.

Keywords: SIRT3; mitochondria; oxidative stress; periodontal disease.