Gao Shuixian, Mu Caiqin, Feng Juan, Sun Xiang
Department of stomatology, The First Hospital of Yulin, Yulin, Shaanxi, China.
PLoS One. 2025 Aug 28;20(8):e0330739. doi: 10.1371/journal.pone.0330739. eCollection 2025.
This study aims to investigate the potential role of miR-146a/Wnt/β-catenin signaling axis in the pathogenesis of periodontitis, using LPS-stimulated hPDLCs as a cell model.
Saliva samples were collected from the subjects and qRT-PCR was used to detect the expression of miR-146a and β-catenin in saliva. Clinical parameters, including probing depth (PD) and attachment loss (AL), were measured and their correlation with miR- 146a and β-catenin levels was determined. Cell proliferation capacity was assessed through CCK-8 assay and the production of inflammatory cytokines was evaluated through ELISA kits. Cell cycle distribution was detected by flow cytometry, and gene expression was detected by qRT-PCR and Western blot.
Our research indicates that compared with the control group, the CP group shows a higher miR-146a expression and a lower β-catenin expression in saliva (P < 0.0001). The expression of miR-146a is positively correlated with AL and PD (P < 0.001), and the expression of β-catenin is negatively correlated with AL and PD (P < 0.001). Inhibiting the expression of miR-146a can promote cell proliferation by regulating cell cycle distribution, reduce the production of inflammatory cytokines, inhibit the expression of p21 and promote the expression of CDK2 and CyclinD1. However, overexpression of miR-146a can result in the opposite effect. In LPS-stimulated hPDLCs, miR-146a expression is up-regulated while β-catenin expression is down-regulated. In addition, overexpression of miR-146a can inhibit β-catenin expression in cells. Simultaneously inhibiting the expression of miR-146a and β-catenin can reverse the effect of inhibiting miR-146a alone on alleviating LPS-induced cell damage.
miR-146a can inhibit LPS-induced damage to hPDLCs by regulating the Wnt/β-catenin signaling pathway.
本研究旨在以脂多糖（LPS）刺激的人牙周膜细胞（hPDLCs）为细胞模型，探讨miR-146a/ Wnt/β-连环蛋白信号轴在牙周炎发病机制中的潜在作用。
收集受试者的唾液样本，采用qRT-PCR检测唾液中miR-146a和β-连环蛋白的表达。测量包括探诊深度（PD）和附着丧失（AL）在内的临床参数，并确定它们与miR-146a和β-连环蛋白水平的相关性。通过CCK-8法评估细胞增殖能力，通过ELISA试剂盒评估炎性细胞因子的产生。通过流式细胞术检测细胞周期分布，通过qRT-PCR和蛋白质免疫印迹法检测基因表达。
我们的研究表明，与对照组相比，慢性牙周炎（CP）组唾液中miR-146a表达较高，β-连环蛋白表达较低（P < 0.0001）。miR-146a的表达与AL和PD呈正相关（P < 0.001），β-连环蛋白的表达与AL和PD呈负相关（P < 0.001）。抑制miR-146a的表达可通过调节细胞周期分布促进细胞增殖，减少炎性细胞因子的产生，抑制p21的表达并促进CDK2和CyclinD1的表达。然而，miR-146a的过表达可导致相反的效果。在LPS刺激的hPDLCs中，miR-146a表达上调而β-连环蛋白表达下调。此外，miR-146a的过表达可抑制细胞中β-连环蛋白的表达。同时抑制miR-146a和β-连环蛋白的表达可逆转单独抑制miR-146a对减轻LPS诱导的细胞损伤的作用。
miR-146a可通过调节Wnt/β-连环蛋白信号通路抑制LPS诱导的hPDLCs损伤。
