胱硫醚 γ-lyase 在高血糖实验性牙周炎中加剧了牙周破坏

IF 4.2 2区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Journal of periodontology Pub Date : 2024-06-28 DOI:10.1002/jper.23-0811
Danni Song, Jiangfeng He, Tianfan Cheng, Lijian Jin, Sijin Li, Beibei Chen, Yongming Li, Chongshan Liao
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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. 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引用次数: 0

摘要

背景糖尿病是牙周炎的主要炎症并发症之一,与牙周炎有双向作用。胱硫醚γ-裂解酶(CTH)是一种合成硫化氢(H2S)的关键内源性酶,CTH/H2S在多种疾病的炎症调节中起着至关重要的作用。本研究旨在探讨高血糖条件下 CTH 在实验性牙周炎中的潜在作用。方法在高糖和牙龈卟啉菌脂多糖(P.g-LPS)条件下培养 CTH 沉默的正常人牙周韧带细胞(hPDLCs)。通过细胞计数试剂盒 8(CCK8)、实时定量聚合酶链反应(RT-qPCR)和酶联免疫吸附试验(ELISA)评估了 CTH 对 hPDLCs 的影响。在 Cth-/- 和野生型(WT)小鼠身上建立了高血糖条件下的实验性牙周炎模型,并通过显微 CT、组织学、RNA-Seq、Western 印迹、抗酒石酸磷酸酶(TRAP)染色和免疫染色来评估牙周破坏的程度。与 WT 小鼠相比,在高血糖条件下患实验性牙周炎的 Cth-/- 小鼠骨质流失减少,白细胞浸润减少,破骨细胞形成受阻,牙周组织中促炎性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。RNA-seq富集改变了健康小鼠牙龈与高血糖实验性牙周炎小鼠的NF-κB通路信号传导。因此,CTH沉默的hPDLCs中p65(P-p65)的磷酸化减轻,导致IL6和TNF的表达减少。CTH敲除抑制了核因子卡巴-B(NF-κB)通路的激活,并减少了高糖和P.g-LPS处理下促炎细胞因子的产生。
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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.
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来源期刊
Journal of periodontology
Journal of periodontology 医学-牙科与口腔外科
CiteScore
9.10
自引率
7.00%
发文量
290
审稿时长
3-8 weeks
期刊介绍: The Journal of Periodontology publishes articles relevant to the science and practice of periodontics and related areas.
期刊最新文献
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