环状PVT1通过调控miR-24-3p/HIF1AN通路促进牙周炎进展。

CircPVT1 promotes periodontitis progression by regulating miR-24-3p/HIF1AN pathway.

作者信息

Bian Yuting, Yu Jingwen, Liu Yang, Shi Yahong, Hou Yujiao, Liu Xin

机构信息

Department of Stomatology, Second Hospital of Shijiazhuang, Shijiazhuang, Hebei, 050000, PR China.

The Affiliated Stomatological Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, PR China.

出版信息

J Stomatol Oral Maxillofac Surg. 2025 Jun;126(3S):102198. doi: 10.1016/j.jormas.2024.102198. Epub 2025 Feb 20.

Abstract

PURPOSE AND BACKGROUND

Periodontitis is a chronic inflammatory oral disease affecting half of the adult population. Circular RNA plays a critical role in periodontitis. CircPVT1(hsa_circ_0085536) was abundant in periodontitis tissues and cells but its mechanism are still unclear. We aim to explore the role of circPVT1 in periodontitis and elucidate how circPVT1 acts.

METHODS

Gingival tissues from patients with periodontitis(n=20) and health participants(n=20) were collected and the expression of circPVT1 was measured by realtime quantitative PCR(RT-qPCR). Cell model for periodontitis was performed by PDLCs treated lipopolysaccharide(LPS). Cell Counting Kit-8(CCK-8), flow cytometry, enzyme-linked immunoabsorbent assay (ELISA), ALP staining and Alizarin red staining were conducted to detect cell viability, apoptosis, inflammatory and oxidative stress factors and osteogenic differentiation. The targeting microRNA(miRNA)/mRNA axis of circPVT1 was predicted and screened.

RESULTS

circPVT1 was upregulated in the gingival tissues of patients with periodontitis. Silencing of circPVT1 inhibited cell viability, decreased inflammatory factors(IL-1β, TNF-α, IL-6) and oxidative stress factors, activated NRF-2 and HO-1 expression and promoted apoptosis and osteoclast differentiation in PDLCs after treated LPS. However, these effects were reversed by transfected miR-24-3p inhibitor and overexpressed of hypoxia-inducible factor 1 subunit alpha inhibitor(HIF1AN) in PDLCs.

CONCLUSION

circPVT1 promotes the progression of periodontitis by modulating NRF-2/HO-1 pathway via the miR-24-3p/HIF1AN axis.

摘要

目的与背景

牙周炎是一种影响半数成年人口的慢性炎症性口腔疾病。环状RNA在牙周炎中起关键作用。CircPVT1(hsa_circ_0085536)在牙周炎组织和细胞中含量丰富,但其机制仍不清楚。我们旨在探讨circPVT1在牙周炎中的作用,并阐明circPVT1的作用方式。

方法

收集牙周炎患者(n = 20)和健康参与者(n = 20)的牙龈组织,通过实时定量PCR(RT-qPCR)检测circPVT1的表达。用脂多糖(LPS)处理人牙周膜细胞(PDLCs)建立牙周炎细胞模型。采用细胞计数试剂盒-8(CCK-8)、流式细胞术、酶联免疫吸附测定(ELISA)、碱性磷酸酶(ALP)染色和茜素红染色检测细胞活力、凋亡、炎症和氧化应激因子以及成骨分化。预测并筛选circPVT1的靶向微小RNA(miRNA)/信使核糖核酸(mRNA)轴。

结果

circPVT1在牙周炎患者牙龈组织中上调。circPVT1沉默抑制了LPS处理后PDLCs的细胞活力,降低了炎症因子(白细胞介素-1β、肿瘤坏死因子-α、白细胞介素-6)和氧化应激因子,激活了核因子E2相关因子2(NRF-2)和血红素加氧酶-1(HO-1)表达,并促进了细胞凋亡和破骨细胞分化。然而,在PDLCs中转染miR-24-3p抑制剂并过表达缺氧诱导因子1α亚基抑制剂(HIF1AN)可逆转这些作用。

结论

circPVT1通过miR-24-3p/HIF1AN轴调节NRF-2/HO-1通路促进牙周炎进展。

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