EGFL6 Promotes Angiogenesis and Odontogenesis in Pulp Regeneration via MAPK Signaling Pathways.

Current stem cell research & therapy Pub Date : 2025-06-04 DOI:10.2174/011574888X362657250528171158

Xiaocui Lu, Yuan Liu, Lin Dai, Bo Cheng, Yanyun Li

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Abstract

Objectives: Epidermal growth factor-like domain-containing protein 6 (EGFL6) is a member of the epidermal growth factor superfamily. It has been reported that it can enhance the osteogenic differentiation potential of stem cells and stimulate angiogenesis. However, its effects on the regulation of odontogenic differentiation of dental pulp stem cells (DPSCs) have not been studied. Therefore, we aimed to investigate the role of EGFL6 in pulp regeneration and its underlying mechanism.

Methods: The cytotoxicity and migration-inductive ability of EGFL6 were evaluated using cell counting kit-8 assay and transwell assay, respectively. A tube formation assay was performed to assess the angiogenic effect of EGFL6. The alkaline phosphatase (ALP) and alizarin red S staining were conducted for mineralization evaluation. The odontoblastic-related and angiogenesis-related markers were measured by quantitative real-time polymerase chain reaction and Western blot analysis. Western blot was also conducted to further examine the levels of key factors involved in MAPK signaling pathways.

Results: EGFL6 displayed no cytotoxicity and was capable of promoting cell migration and angiogenesis. Besides, EGFL6 enhanced the mineralization process and up-regulated the expression levels of odontoblastic-related markers (DSPP, DMP1, and BSP) after 5, 7, and 10 days. The expression levels of odontoblastic-related and angiogenesis-related proteins (DSPP, DMP1, VEGF, and ALP) could all be up-regulated by EGFL6. There was also an increase in the phosphorylation levels of ERK1/2 and P38.

Conclusion: EGFL6 can promote the migration, angiogenesis, and odontogenesis differentiation of DPSCs via the activation of MAPK signaling pathways.

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EGFL6通过MAPK信号通路促进牙髓再生中的血管生成和牙髓生成。

目的：表皮生长因子样结构域蛋白6 （Epidermal growth factor-like domain containing protein 6, EGFL6）是表皮生长因子超家族的一员。据报道，它可以增强干细胞的成骨分化潜能，刺激血管生成。然而，其对牙髓干细胞（DPSCs）成牙分化的调控作用尚未见研究。因此，我们旨在研究EGFL6在牙髓再生中的作用及其潜在机制。方法：分别采用细胞计数试剂盒-8法和transwell法评价EGFL6的细胞毒性和诱导迁移能力。通过管形成实验来评估EGFL6的血管生成作用。碱性磷酸酶（ALP）和茜素红S染色进行矿化评价。采用实时定量聚合酶链反应和Western blot检测成牙细胞相关和血管新生相关标志物。Western blot还进一步检测了MAPK信号通路中涉及的关键因子的水平。结果：EGFL6无细胞毒性，能促进细胞迁移和血管生成。此外，EGFL6在5、7、10天后增强矿化过程，上调成牙细胞相关标志物（DSPP、DMP1、BSP）的表达水平。EGFL6可上调成牙细胞相关蛋白和血管生成相关蛋白（DSPP、DMP1、VEGF、ALP）的表达水平。ERK1/2和P38的磷酸化水平也有所升高。结论：EGFL6可通过激活MAPK信号通路促进DPSCs的迁移、血管生成和成牙分化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Current stem cell research & therapy

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