LncRNA MIAT 在牙周炎中的诊断意义以及通过 miR-204-5p/DKK1 轴影响牙周韧带成纤维细胞的分子机制

IF 2.2 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Archives of oral biology Pub Date : 2024-08-04 DOI:10.1016/j.archoralbio.2024.106066
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引用次数: 0

摘要

本研究探讨了长非编码 RNA 心肌梗死相关转录本(MIAT)在牙周炎中的临床重要性及其对人牙周韧带成纤维细胞(hPDLFs)功能调控的影响。使用牙龈卟啉单胞菌脂多糖(Pg-LPS)刺激 hPDLFs,建立体外细胞模型。实时定量聚合酶链反应用于测量 MIAT 和成骨因子的 mRNA 水平。使用酶联免疫吸附试验评估炎症因子的浓度。通过细胞计数试剂盒-8 和流式细胞术检测细胞活力和凋亡。结果 在牙周炎患者和 Pg-LPS 诱导的 hPDLFs 的牙龈沟液中发现了高表达的 MIAT 和 Dicckopf-1 (DDK1),以及低表达的 miR-204-5p。MIAT 对从健康人中识别牙周炎患者的灵敏度为 76.53%,特异度为 86.49%。MIAT 是 miR-204-5p 的海绵,能上调 DDK1 mRNA 的表达。沉默 MIAT 可减少 Pg-LPS 对 hPDLFs 细胞凋亡和炎症的促进作用,并增强成骨分化。然而,miR-204-5p抑制剂能明显逆转沉默MIAT的效果。它通过聚焦于 miR-204-5p/DKK1 轴来调节 PDLFs 的凋亡、炎症和成骨分化,表明它有可能成为治疗牙周炎的新靶点。
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Diagnostic significance of LncRNA MIAT in periodontitis and the molecular mechanisms influencing periodontal ligament fibroblasts via the miR-204-5p/DKK1 axis

Objective

This study investigated the clinical importance of long noncoding RNA myocardial infarction-associated transcript (MIAT) in periodontitis and its impact on the functional regulation of human periodontal ligament fibroblasts (hPDLFs).

Methods

Ninety-eight periodontitis patients and 74 healthy controls were enrolled. In vitro cellular models were created using Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) to stimulate hPDLFs. Real-time quantitative polymerase chain reaction was used to measure mRNA levels of MIAT and osteogenic factors. Inflammation factor concentration was assessed using an enzyme-linked immunosorbent assay. Cell viability and apoptosis were examined by cell counting kit −8 and flow cytometry assay. The targeting relationship was verified by the dual-luciferase reporter and RNA Immunoprecipitation assay.

Results

Highly expressed MIAT and Dicckopf-1 (DDK1), and lowly expressed miR-204–5p were found in the gingival crevicular fluid of periodontitis patients and Pg-LPS induced hPDLFs. MIAT has a sensitivity of 76.53 % and a specificity of 86.49 % for identifying patients with periodontitis among healthy individuals. MIAT acts as a sponge for miR-204–5p and upregulates DDK1 mRNA expression. Silencing of MIAT diminished the promotion of apoptosis and inflammation in hPDLFs by Pg-LPS and enhanced osteogenic differentiation. However, a miR-204–5p inhibitor significantly reversed the effect of silenced MIAT.

Conclusions

MIAT may act as a promising biomarker for periodontitis. It modulates apoptosis, inflammation, and osteogenic differentiation of PDLFs by focusing on the miR-204–5p/DKK1 axis, indicating its potential as a new therapeutic target for treating periodontitis.

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来源期刊
Archives of oral biology
Archives of oral biology 医学-牙科与口腔外科
CiteScore
5.10
自引率
3.30%
发文量
177
审稿时长
26 days
期刊介绍: Archives of Oral Biology is an international journal which aims to publish papers of the highest scientific quality in the oral and craniofacial sciences. The journal is particularly interested in research which advances knowledge in the mechanisms of craniofacial development and disease, including: Cell and molecular biology Molecular genetics Immunology Pathogenesis Cellular microbiology Embryology Syndromology Forensic dentistry
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