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LncRNA OIP5-AS1 通过海绵吸附 miR-92a-3p 抑制脂多糖诱导的人牙周膜细胞炎症反应并促进成骨分化。

LncRNA OIP5-AS1 inhibits the lipopolysaccharide-induced inflammatory response and promotes osteogenic differentiation of human periodontal ligament cells by sponging miR-92a-3p.

机构信息

Dental Department, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shanxi 710077, P.R. China.

Second Clinical Division, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing 100081, P.R. China.

出版信息

Bioengineered. 2022 May;13(5):12055-12066. doi: 10.1080/21655979.2022.2067291.

Abstract

Periodontitis is a chronic infectious disease that affects the oral health of adults. Long non-coding RNA OIP5 antisense RNA 1 (OIP5-AS1) has been reported to downregulated in the periodontal tissue of patients with periodontitis. Therefore, the study sought to look at the possible functions of OIP5-AS1 in periodontitis and the associated underlying mechanisms. In the present study, the expression level of OIP5-AS1 and microRNA-92a-3p were analyzed using reverse transcription-quantitative PCR. The levels of osteogenic proteins were determined using western blotting and inflammatory cytokines and oxidative stress were also examined. The proliferation of human periodontal ligament stem cells (hPDLSCs) was evaluated using MTT assays. Assay of osteogenic differentiation was undertaken by means of Alkaline phosphatase staining. The possible association between OIP5-AS1 and miR-92a-3p was determined applying dual-luciferase reporter assays and verified by RNA immunoprecipitation assay. We found that OIP5-AS1 was expressed at low levels in lipopolysaccharide (LPS)-stimulated hPDLSCs. OIP5-AS1 overexpression promoted proliferation and osteogenic differentiation ability and reduced LPS-induced inflammation in hPDLSCs. Furthermore, OIP5-AS1 directly targeted and reduced miR-92a-3p expression. The overexpression of miR-92a-3p partly abolished the effects of OIP5-AS1 on LPS-induced cell proliferation and osteogenic differentiation as well as inflammation in hPDLSCs. Collectively, the results indicated that OIP5-AS1 overexpression inhibited the LPS-induced inflammatory response and promoted the osteogenic differentiation of hPDLSCs by sponging miR-92a-3p. Thus, OIP5-AS1 is probably an essential objective for research during periodontitis treatment.

摘要

牙周炎是一种影响成年人口腔健康的慢性传染病。据报道,长链非编码 RNA OIP5 反义 RNA 1(OIP5-AS1)在牙周炎患者的牙周组织中下调。因此,本研究旨在探讨 OIP5-AS1 在牙周炎中的可能功能及其相关的潜在机制。在本研究中,采用逆转录定量 PCR 分析 OIP5-AS1 和 microRNA-92a-3p 的表达水平。采用 Western blot 检测成骨蛋白水平,同时检测炎症细胞因子和氧化应激。采用 MTT 法评估人牙周膜干细胞(hPDLSCs)的增殖。通过碱性磷酸酶染色进行成骨分化检测。采用双荧光素酶报告基因检测和 RNA 免疫沉淀试验确定 OIP5-AS1 与 miR-92a-3p 之间的可能关联。我们发现 LPS 刺激的 hPDLSCs 中 OIP5-AS1 表达水平较低。OIP5-AS1 过表达促进 hPDLSCs 的增殖和成骨分化能力,并降低 LPS 诱导的炎症。此外,OIP5-AS1 直接靶向并降低 miR-92a-3p 的表达。miR-92a-3p 的过表达部分消除了 OIP5-AS1 对 LPS 诱导的 hPDLSCs 增殖、成骨分化和炎症的影响。总之,结果表明 OIP5-AS1 过表达通过海绵吸附 miR-92a-3p 抑制 LPS 诱导的炎症反应,促进 hPDLSCs 的成骨分化。因此,OIP5-AS1 可能是牙周炎治疗研究的重要目标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b96/9276041/7a2fa29d1de7/KBIE_A_2067291_UF0001_B.jpg

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