Cystathionine γ‐lyase contributes to exacerbation of periodontal destruction in experimental periodontitis under hyperglycemia

Abstract

AbstractBackgroundDiabetes 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.