{"title":"胱硫醚 γ-lyase 在高血糖实验性牙周炎中加剧了牙周破坏","authors":"Danni Song, Jiangfeng He, Tianfan Cheng, Lijian Jin, Sijin Li, Beibei Chen, Yongming Li, Chongshan Liao","doi":"10.1002/jper.23-0811","DOIUrl":null,"url":null,"abstract":"BackgroundDiabetes is one of the major inflammatory comorbidities of periodontitis via 2‐way interactions. Cystathionine γ‐lyase (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.MethodsCTH‐silenced 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>‐LPS) condition. The effects of CTH on hPDLCs were assessed by Cell Counting Kit 8 (CCK8), real‐time quantitative polymerase chain reaction (RT‐qPCR), and enzyme‐linked immunosorbent assay (ELISA). The model of experimental periodontitis under hyperglycemia was established on both <jats:italic>Cth</jats:italic><jats:sup>−/−</jats:sup> and wild‐type (WT) mice, and the extent of periodontal destruction was assessed by micro‐CT, histology, RNA‐Seq, Western blot, tartrate‐resistant acid phosphatase (TRAP) staining and immunostaining.Results<jats:italic>CTH</jats:italic> mRNA expression increased in hPDLCs in response to increasing concentration of <jats:italic>P.g</jats:italic>‐LPS stimulation in a high glucose medium. With reference to WT mice<jats:italic>, Cth</jats:italic><jats:sup>−/−</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‐6 (IL‐6) and tumor necrosis factor alpha (TNF‐α) in periodontal tissue. RNA‐seq‐enriched altered NF‐κB pathway signaling in healthy murine gingiva with experimental periodontitis mice under hyperglycemia. Accordingly, phosphorylation of p65 (P‐p65) was alleviated in <jats:italic>CTH</jats:italic>‐silenced 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‐B (NF‐κB) pathway and decreased production of proinflammatory cytokines under high glucose and <jats:italic>P.g</jats:italic>‐LPS treatment.ConclusionThe present findings suggest the potential of CTH as a therapeutic target for tackling periodontitis in diabetic patients.","PeriodicalId":16716,"journal":{"name":"Journal of periodontology","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cystathionine γ‐lyase contributes to exacerbation of periodontal destruction in experimental periodontitis under hyperglycemia\",\"authors\":\"Danni Song, Jiangfeng He, Tianfan Cheng, Lijian Jin, Sijin Li, Beibei Chen, Yongming Li, Chongshan Liao\",\"doi\":\"10.1002/jper.23-0811\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"BackgroundDiabetes is one of the major inflammatory comorbidities of periodontitis via 2‐way interactions. Cystathionine γ‐lyase (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.MethodsCTH‐silenced 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>‐LPS) condition. The effects of CTH on hPDLCs were assessed by Cell Counting Kit 8 (CCK8), real‐time quantitative polymerase chain reaction (RT‐qPCR), and enzyme‐linked immunosorbent assay (ELISA). The model of experimental periodontitis under hyperglycemia was established on both <jats:italic>Cth</jats:italic><jats:sup>−/−</jats:sup> and wild‐type (WT) mice, and the extent of periodontal destruction was assessed by micro‐CT, histology, RNA‐Seq, Western blot, tartrate‐resistant acid phosphatase (TRAP) staining and immunostaining.Results<jats:italic>CTH</jats:italic> mRNA expression increased in hPDLCs in response to increasing concentration of <jats:italic>P.g</jats:italic>‐LPS stimulation in a high glucose medium. With reference to WT mice<jats:italic>, Cth</jats:italic><jats:sup>−/−</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‐6 (IL‐6) and tumor necrosis factor alpha (TNF‐α) in periodontal tissue. RNA‐seq‐enriched altered NF‐κB pathway signaling in healthy murine gingiva with experimental periodontitis mice under hyperglycemia. Accordingly, phosphorylation of p65 (P‐p65) was alleviated in <jats:italic>CTH</jats:italic>‐silenced 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‐B (NF‐κB) pathway and decreased production of proinflammatory cytokines under high glucose and <jats:italic>P.g</jats:italic>‐LPS treatment.ConclusionThe present findings suggest the potential of CTH as a therapeutic target for tackling periodontitis in diabetic patients.\",\"PeriodicalId\":16716,\"journal\":{\"name\":\"Journal of periodontology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-06-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of periodontology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/jper.23-0811\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of periodontology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/jper.23-0811","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
Cystathionine γ‐lyase contributes to exacerbation of periodontal destruction in experimental periodontitis under hyperglycemia
BackgroundDiabetes is one of the major inflammatory comorbidities of periodontitis via 2‐way interactions. Cystathionine γ‐lyase (CTH) is a pivotal endogenous enzyme synthesizing hydrogen sulfide (H2S), and CTH/H2S 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.MethodsCTH‐silenced and normal human periodontal ligament cells (hPDLCs) were cultured in a high glucose and Porphyromonas gingivalis lipopolysaccharide (P.g‐LPS) condition. The effects of CTH on hPDLCs were assessed by Cell Counting Kit 8 (CCK8), real‐time quantitative polymerase chain reaction (RT‐qPCR), and enzyme‐linked immunosorbent assay (ELISA). The model of experimental periodontitis under hyperglycemia was established on both Cth−/− and wild‐type (WT) mice, and the extent of periodontal destruction was assessed by micro‐CT, histology, RNA‐Seq, Western blot, tartrate‐resistant acid phosphatase (TRAP) staining and immunostaining.ResultsCTH mRNA expression increased in hPDLCs in response to increasing concentration of P.g‐LPS stimulation in a high glucose medium. With reference to WT mice, Cth−/− 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‐6 (IL‐6) and tumor necrosis factor alpha (TNF‐α) in periodontal tissue. RNA‐seq‐enriched altered NF‐κB pathway signaling in healthy murine gingiva with experimental periodontitis mice under hyperglycemia. Accordingly, phosphorylation of p65 (P‐p65) was alleviated in CTH‐silenced hPDLCs, leading to decreased expression of IL6 and TNF. CTH knockdown inhibited activation of nuclear factor kappa‐B (NF‐κB) pathway and decreased production of proinflammatory cytokines under high glucose and P.g‐LPS treatment.ConclusionThe present findings suggest the potential of CTH as a therapeutic target for tackling periodontitis in diabetic patients.