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Cystathionine \u03b3\u2010lyase (CTH) is a pivotal endogenous enzyme synthesizing hydrogen sulfide (H<jats:sub>2<\/jats:sub>S), and CTH\/H<jats:sub>2<\/jats:sub>S is crucially implicated in modulating inflammation in various diseases. This study aimed to explore the potential role of CTH in experimental periodontitis under a hyperglycemic condition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CTH\u2010silenced and normal human periodontal ligament cells (hPDLCs) were cultured in a high glucose and <jats:italic>Porphyromonas gingivalis<\/jats:italic> lipopolysaccharide (<jats:italic>P.g<\/jats:italic>\u2010LPS) condition. The effects of CTH on hPDLCs were assessed by Cell Counting Kit 8 (CCK8), real\u2010time quantitative polymerase chain reaction (RT\u2010qPCR), and enzyme\u2010linked immunosorbent assay (ELISA). The model of experimental periodontitis under hyperglycemia was established on both <jats:italic>Cth<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> and wild\u2010type (WT) mice, and the extent of periodontal destruction was assessed by micro\u2010CT, histology, RNA\u2010Seq, Western blot, tartrate\u2010resistant acid phosphatase (TRAP) staining and immunostaining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>CTH<\/jats:italic> mRNA expression increased in hPDLCs in response to increasing concentration of <jats:italic>P.g<\/jats:italic>\u2010LPS stimulation in a high glucose medium. With reference to WT mice<jats:italic>, Cth<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice with experimental periodontitis under hyperglycemia exhibited reduced bone loss, decreased leukocyte infiltration and hindered osteoclast formation, along with reduced expression of proinflammatory cytokines interleukin\u20106 (IL\u20106) and tumor necrosis factor alpha (TNF\u2010\u03b1) in periodontal tissue. RNA\u2010seq\u2010enriched altered NF\u2010\u03baB pathway signaling in healthy murine gingiva with experimental periodontitis mice under hyperglycemia. Accordingly, phosphorylation of p65 (P\u2010p65) was alleviated in <jats:italic>CTH<\/jats:italic>\u2010silenced hPDLCs, leading to decreased expression of <jats:italic>IL6<\/jats:italic> and <jats:italic>TNF<\/jats:italic>. <jats:italic>CTH<\/jats:italic> knockdown inhibited activation of nuclear factor kappa\u2010B (NF\u2010\u03baB) pathway and decreased production of proinflammatory cytokines under high glucose and <jats:italic>P.g<\/jats:italic>\u2010LPS treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The present findings suggest the potential of CTH as a therapeutic target for tackling periodontitis in diabetic patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jper.23-0811","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T23:50:20Z","timestamp":1719532220000},"page":"255-267","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cystathionine \u03b3\u2010lyase contributes to exacerbation of periodontal destruction in experimental periodontitis under hyperglycemia"],"prefix":"10.1002","volume":"96","author":[{"given":"Danni","family":"Song","sequence":"first","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration &amp; Tongji Research Institute of Stomatology &amp; Department of Orthodontics Stomatological Hospital and Dental School Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiangfeng","family":"He","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration &amp; Tongji Research Institute of Stomatology &amp; Department of Orthodontics Stomatological Hospital and Dental School Tongji University  Shanghai 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