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Abstract：
It has been reported that protein arginine methyltransferase 5 (PRMT5) serves a significant role in osteogenic differentiation and inflammatory response. Nevertheless, its role in periodontitis as well as its underlying mechanism remain to be elucidated. The aim of the present study was to explore the role of PRMT5 in periodontitis and whether PRMT5 could reduce liposaccharide (LPS)-induced inflammation of human periodontal ligament stem cells (hPDLSCs) and promote osteogenic differentiation through STAT3/NF-κB signaling. In the current study, the expression levels of PRMT5 were determined in LPS-induced hPDLSCs by reverse transcription-quantitative PCR and western blot analysis. ELISA and western blot analysis were employed to assess the secretion and expression levels of inflammatory factors, respectively. The osteogenic differentiation and mineralization potential of hPDLSCs were evaluated using alkaline phosphatase (ALP) activity assay, Alizarin red staining and western blot analysis. Additionally, western blot analysis was applied to determine the expression levels of the STAT3/NF-κB signaling pathway-related proteins. The results showed that the expression levels of PRMT5 were significantly enhanced in LPS-induced hPDLSCs. Additionally, PRMT5 knockdown reduced the contents of IL-1β, IL-6, TNF-α, inducible nitric oxide synthase and cyclooxygenase-2. PRMT5 depletion also enhanced ALP activity, improved the mineralization ability and upregulated bone morphogenetic protein 2, osteocalcin and runt-related transcription factor 2 in LPS-induced hPDLSCs. Furthermore, PRMT5 knockdown inhibited inflammation and promoted the osteogenic differentiation of hPDLSCs via blocking the activation of the STAT3/NF-κB signaling pathway. In conclusion, PRMT5 inhibition suppressed LPS-induced inflammation and accelerated osteogenic differentiation in hPDLSCs via regulating STAT3/NF-κB signaling, thus providing a potential targeted therapy for the improvement of periodontitis.
摘要：
据报道，蛋白质精氨酸甲基转移酶5（PRMT5）在成骨分化和炎症反应中起重要作用。然而，其在牙周炎中的作用及其潜在机制仍有待阐明。本研究的目的是探讨PRMT5在牙周炎中的作用以及PRMT5是否可以通过STAT3/NF-κB信号通路减轻脂多糖(LPS)诱导的人牙周膜干细胞(hPDLSCs)炎症反应并促进成骨分化。在目前的研究中,通过逆转录-定量PCR和Westernblot分析测定LPS诱导的hPDLSCs中PRMT5的表达水平.ELISA和Westernblot分析炎症因子的分泌和表达水平。分别。用碱性磷酸酶(ALP)活性测定评价hPDLSCs的成骨分化和矿化潜能,茜素红染色和蛋白质印迹分析。此外,应用蛋白质印迹分析确定STAT3/NF-κB信号通路相关蛋白的表达水平。结果显示,在LPS诱导的hPDLSCs中PRMT5的表达水平显著增强。此外,PRMT5敲低可降低IL-1β的含量,IL-6,TNF-α,诱导型一氧化氮合酶和环氧合酶-2。PRMT5耗竭也增强了ALP活性，在LPS诱导的hPDLSCs中提高了矿化能力，并上调了骨形态发生蛋白2，骨钙蛋白和runt相关转录因子2。此外，PRMT5敲低通过阻断STAT3/NF-κB信号通路的激活，抑制炎症反应并促进hPDLSCs的成骨分化。总之,抑制PRMT5通过调节STAT3/NF-κB信号抑制LPS诱导的炎症和促进hPDLSCs成骨分化,从而为牙周炎的改善提供了潜在的靶向治疗。
