Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, No. 56, Lingyuan West Road, Guangzhou, 510055, China.
Exp Cell Res. 2021 Mar 15;400(2):112495. doi: 10.1016/j.yexcr.2021.112495. Epub 2021 Jan 29.
Pulpitis refers to inflammation of the inner pulp by invading microbes, and tissue repair occurs due to odontogenic differentiation of human dental pulp cells (hDPCs) with multidifferentiation potential. Long noncoding RNAs (lncRNAs) can modulate numerous pathological and biological processes; however, the role of lncRNAs in the inflammation and regeneration of the dentin-pulp complex in pulpitis is unclear. Here, we performed high-throughput sequencing to identify differentially expressed lncRNAs between human normal and inflamed pulp and concluded that lncMEG3 (lncRNA maternally expressed gene 3, MEG3) was significantly upregulated in both inflamed pulp and LPS-treated hDPCs. MEG3 expression in the pulp tissue was detected using the RNAscope® technique. RNA pulldown assays identified the MEG3-interacting proteins and the potential mechanisms. With MEG3 knockdown, we investigated the role of MEG3 in the secretion of inflammatory cytokines in LPS-treated hDPCs and odontogenic differentiation of hDPCs. MEG3 downregulation inhibited the secretion of TNF-α, IL-1β and IL-6 in LPS-treated hDPCs, and the p38/MAPK signaling pathway may be related to this effect. MEG3 knockdown promoted odontogenic differentiation of hDPCs by regulating the Wnt/β-catenin signaling pathway. Our study suggested that MEG3 has a negative effect on inflammation and regeneration of the dentin-pulp complex in pulpitis.
牙髓炎是指微生物入侵引起的牙髓内组织炎症，而人牙髓细胞（hDPCs）具有多向分化潜能，通过odontogenic 分化进行组织修复。长链非编码 RNA（lncRNAs）可以调节许多病理和生物学过程；然而，lncRNAs 在牙髓炎中牙本质-牙髓复合体的炎症和再生中的作用尚不清楚。在这里，我们进行了高通量测序，以鉴定人正常和发炎牙髓之间差异表达的 lncRNAs，并得出结论，lncMEG3（lncRNA maternally expressed gene 3，MEG3）在发炎牙髓和 LPS 处理的 hDPCs 中均显著上调。使用 RNAscope®技术检测牙髓组织中的 MEG3 表达。RNA 下拉测定鉴定了 MEG3 相互作用蛋白及其潜在机制。通过 MEG3 敲低，我们研究了 MEG3 在 LPS 处理的 hDPCs 中炎症细胞因子分泌和 hDPCs 牙源性分化中的作用。MEG3 下调抑制了 LPS 处理的 hDPCs 中 TNF-α、IL-1β 和 IL-6 的分泌，p38/MAPK 信号通路可能与这种效应有关。MEG3 下调通过调节 Wnt/β-catenin 信号通路促进 hDPCs 的牙源性分化。我们的研究表明，MEG3 对牙髓炎中牙本质-牙髓复合体的炎症和再生有负面影响。
