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 : 2024-06-27 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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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

Background

Diabetes 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.

Methods

CTH-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.

Results

CTH 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.