Wnt Signaling Activation in Gingival Epithelial Cells and Macrophages of Experimental Periodontitis.
Wnt Signaling Activation in Gingival Epithelial Cells and Macrophages of Experimental Periodontitis.
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牙龈上皮细胞和实验牙周炎的巨噬细胞中的Wnt信号传导激活。
DOI：
10.3390/dj11050129
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发表时间：
2023-05-09
影响因子：
2.6
通讯作者：
中科院分区：
文献类型：
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作者：
目的：Wingless/integrated (Wnt) 信号在维持环境稳态中发挥着关键作用，并且还参与炎症性疾病的发病机制。然而，其在牙周炎期间巨噬细胞中的作用尚不清楚。本研究旨在探讨牙周炎背景下 Wnt 信号传导与巨噬细胞之间的相互作用。方法：使用牙龈卟啉单胞菌 (P.g) 相关结扎线在 C57/BL6 小鼠中诱导实验性牙周炎 14 天。采用免疫组织化学方法研究牙周组织中促炎细胞因子肿瘤坏死因子 (TNF-α) 的表达、β-连环蛋白的稳定性和巨噬细胞标记物 F4/80。在经过 Wnt3a 条件培养基刺激的 Raw 264.7 小鼠巨噬细胞中，使用蛋白质印迹分析检查 Wnt 信号传导对 TNF-α 的影响（有或没有 Wnt3a 抗体中和），并与原代培养的牙龈上皮细胞 (GEC) 进行比较。通过分析 Wnt 信号通路的关键组成部分，包括 GEC 和 Raw 264.7 细胞中低密度脂蛋白受体相关蛋白 (LRP) 6 的活性和 β-catenin 的核积累，评估 P.g 脂多糖 (LPS) 对 Wnt 信号传导的影响。结果：P.g 相关结扎引起的牙周炎小鼠牙龈巨噬细胞中 TNF-α 和活化的 β-catenin 过度表达。 TNF-α和活化的β-catenin的表达模式与F4/80的表达模式一致。在 Raw 264.7 细胞中，Wnt 信号通路的激活导致 TNF-α 增加，但在 GEC 中未观察到这种效应。此外，LPS 处理诱导 Raw 264.7 细胞中 β-catenin 积累和 LRP6 激活，但添加 Dickkopf-1 (DKK1) 可以阻断这一现象。结论：实验性牙周炎巨噬细胞中 Wnt 信号异常激活。巨噬细胞中 Wnt 信号的激活可能在牙周炎中发挥促炎作用。针对特定信号通路（例如 Wnt 通路）可能有望开发新的牙周炎治疗干预措施。
Objective: Wingless/integrated (Wnt) signaling plays critical roles in maintaining environmental homeostasis and is also involved in the pathogenesis of inflammatory diseases. However, its role in macrophages during periodontitis is not well understood. The present study aims to investigate the interaction between Wnt signaling and macrophages in the context of periodontitis. Methods: Experimental periodontitis was induced in C57/BL6 mice using a Porphyromonas gingivalis (P.g)-associated ligature for 14 days. Immunohistochemistry was performed to study the expression of the pro-inflammatory cytokine tumor necrosis factor (TNF-α), the stabilization of β-catenin, and the macrophage marker F4/80 in the periodontal tissues. The effect of Wnt signaling on TNF-α was examined using Western blot analysis in Raw 264.7 murine macrophages stimulated by Wnt3a-conditioned medium, with or without Wnt3a antibody neutralization, and compared with primary cultured gingival epithelial cells (GECs). The effect of P.g lipopolysaccharide (LPS) on Wnt signaling was assessed by analyzing key components of the Wnt signaling pathway, including the activity of low-density lipoprotein receptor-related protein (LRP) 6 and nuclear accumulation of β-catenin in GEC and Raw 264.7 cells. Results: Over-expressions of TNF-α and activated β-catenin were presented in the macrophages in the gingiva from mice with P.g-associated ligature-induced periodontitis. The expression patterns of TNF-α and activated β-catenin were consistent with the expression of F4/80. In Raw 264.7 cells, activation of the Wnt signaling pathway led to an increase in TNF-α, but this effect was not observed in GEC. Additionally, treatment with LPS induced β-catenin accumulation and LRP6 activation in Raw 264.7 cells, which were blocked by the addition of Dickkopf-1(DKK1). Conclusions: Wnt signaling was aberrantly activated in the macrophages in experimental periodontitis. The activation of Wnt signaling in the macrophages may play a pro-inflammatory role in periodontitis. Targeting specific signaling pathways, such as the Wnt pathway, may hold promise for developing novel therapeutic interventions for periodontitis.
影响因子：
2.7
作者：
Chen, Ying;Jiang, Zheqing;Keohane, Ana;Hu, Yang
通讯作者：
Hu, Yang