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.

中文翻译：

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胱硫醚γ-裂解酶导致高血糖下实验性牙周炎牙周破坏加剧


背景糖尿病是牙周炎的主要炎症合并症之一，通过双向相互作用。胱硫醚γ-裂解酶（CTH）是合成硫化氢（H 2 S) 和 CTH/H 2 S 在调节各种疾病的炎症方面发挥着至关重要的作用。本研究旨在探讨CTH在高血糖条件下实验性牙周炎中的潜在作用。方法CTH沉默和正常人牙周膜细胞（hPDLCs）在高糖和牙龈卟啉单胞菌脂多糖（ PG ‐LPS）条件。通过细胞计数试剂盒 8 (CCK8)、实时定量聚合酶链反应 (RT-qPCR) 和酶联免疫吸附测定 (ELISA) 评估 CTH 对 hPDLC 的影响。建立高血糖下实验性牙周炎模型Cth −/−和野生型（WT）小鼠，并通过显微CT、组织学、RNA-Seq、蛋白质印迹、抗酒石酸酸性磷酸酶（TRAP）染色和免疫染色评估牙周破坏的程度。 结果甲状腺激素hPDLCs 中 mRNA 表达随着浓度的增加而增加PG ‐高葡萄糖培养基中的 LPS 刺激。参考WT小鼠, Cth −/−高血糖下患有实验性牙周炎的小鼠表现出骨质流失减少、白细胞浸润减少、破骨细胞形成受阻，同时牙周组织中促炎细胞因子白细胞介素-6 (IL-6) 和肿瘤坏死因子 α (TNF-α) 的表达减少。 在高血糖下患有实验性牙周炎的健康小鼠牙龈中，RNA-seq 富集改变了 NF-κB 通路信号传导。因此，p65 (P-p65) 的磷酸化在甲状腺激素‐沉默 hPDLC，导致表达减少白细胞介素6和肿瘤坏死因子。甲状腺激素敲除抑制核因子 kappa-B (NF-κB) 通路的激活并减少高糖和高糖条件下促炎细胞因子的产生PG ‐LPS 治疗。结论目前的研究结果表明 CTH 作为治疗糖尿病患者牙周炎的治疗靶点的潜力。