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Sirtuin 3 (Sirt3) is a NAD<jats:sup>+<\/jats:sup>\u2010dependent protein deacetylase contributing to mitochondrial homeostasis and various cell functions. In this study, the expression of Sirt3 in cementoblasts was found to be increased during cementoblast mineralisation and cementum development, while it decreased gradually under P.g. infection in a multiplicity of infection\u2010dependent manner. Compared with wild type mice, the Sirt3 knockout mice showed less cellular cementum and lower mineralisation capacity with decreased expression of Runx2 and OCN in cementoblasts. Sirt3 inhibition by 3\u2010TYP or Sirt3 silencing by lentivirus infection both confirmed the impaired cementogenesis. Conversely, honokiol (HKL) was simulated to bind Sirt3 and was applied to activate Sirt3 in cementoblasts. HKL\u2010mediated Sirt3 activation facilitated cementoblast mineralisation and rescued P.g.\u2010suppressed cementoblast mineralisation markedly. Superoxide dismutase 2 (SOD2), the downstream molecule of Sirt3, showed a similar expression pattern to Sirt3 under different conditions. Silencing of SOD2 was demonstrated to restrain cementoblast mineralisation. The pan acetylation was detected to decrease under Sirt3\u2010upregulating conditions and increase under Sirt3\u2010downregulating conditions. The binding of Sirt3 and SOD2 in cementoblasts was also verified. Furthermore, SOD2 acetylation and specific SOD2\u2010K68 acetylation were found to be upregulated under P.g. or Sirt3 silencing conditions and downregulated by HKL stimulation. Moreover, K68Q mutation simulating acetylation decreased cementoblast mineralisation, while K68R mutation simulating deacetylation increased it. Altogether, Sirt3 deacetylates SOD2 via K68 to orchestrate P.g.\u2010perturbed cementogenesis, and HKL is a Sirt3\u2010targeted treatment candidate.<\/jats:p>","DOI":"10.1111\/cpr.70022","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T01:16:53Z","timestamp":1741742213000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Sirt3 Rescues <i>Porphyromonas gingivalis<\/i>\u2010Impaired Cementogenesis via <scp>SOD2<\/scp> Deacetylation"],"prefix":"10.1111","volume":"58","author":[{"given":"Xin","family":"Huang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology School &amp; Hospital of Stomatology, Wuhan University  Wuhan China"},{"name":"Department of Periodontology School &amp; Hospital of Stomatology, Wuhan 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