Work

Sirt3-Mediated Metabolic Reprogramming Regulates Osteoclast Differentiation Affecting Periodontitis

Year: 2025

Type: article

Abstract: This study aims to elucidate how SIRT3 modulates periodontitis through acetylation-dependent metabolic reprogramming Periodontitis was induced in C57BL/6 mice via ligature placemen, with SIRT3 expression quantified by qPCR and immunofluorescence. In vitro, bone marrow-derived osteoclasts were treated with LPS or MG132 (proteasome inhibitor), followed by ubiquitination assays (co-immunoprecipitation). We identified SIRT3-interacting proteins through mass spectrometry and validated their status as SIRT3 substrates via acetylation assays. Glycolytic flux and osteoclast differentiation (TRAP staining/Western blot) were assessed, with SIRT3 overexpression rescue experiments performed using lentiviral transduction. In a murine periodontitis model, SIRT3 expression was significantly downregulated in periodontal tissues compared to healthy controls. Mechanistically, LPS stimulation induced ubiquitination-mediated degradation of SIRT3 in osteoclasts, as evidenced by proteasomal inhibition assays.SIRT3 deficiency led to hyperacetylation of its mitochondrial substrates, thereby enhancing glycolysis and driving osteoclast differentiation. SIRT3 deficiency promotes osteoclastogenesis via acetylated substrate-driven glycolysis, positioning SIRT3 as a therapeutic node to halt bone resorption.

Source: International Dental Journal

DOI: 10.1016/j.identj.2025.104652

Author: Jiahui Zhong

Institutions: Zhejiang University Medical College Affiliated Stomatological Hospital, Zhejiang University

Language: English

Topic: Sirtuins and Resveratrol in Medicine

Subfield: Geriatrics and Gerontology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,550