Stromal-derived Factor-1 alpha signaling is involved in bone morphogenetic protein-2-induced odontogenic differentiation of stem cells from apical papilla via the Smad and Erk signaling pathways
Stromal-derived Factor-1 alpha signaling is involved in bone morphogenetic protein-2-induced odontogenic differentiation of stem cells from apical papilla via the Smad and Erk signaling pathways
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基质衍生因子 1 α 信号传导通过 Smad 和 Erk 信号通路参与骨形态发生蛋白 2 诱导的根尖乳头干细胞的牙源性分化
DOI：
10.1016/j.yexcr.2019.04.036
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发表时间：
2019
影响因子：
3.7
通讯作者：
Yu Qing
中科院分区：
文献类型：
--
作者：
Xiao Min;Yao Bo;Zhang Bei di;Bai Yu;Sui Wen;Wang Wei;Yu Qing
基质衍生因子-1 α（SDF-1α）是一种趋化因子信号分子，与跨膜受体CXC趋化因子受体4（CXCR 4）结合，在发育组织稳态中发挥重要作用。SDF-1α信号通过CXCR 4调节干细胞和前体细胞的募集，以支持组织特异性修复或再生。本研究探讨SDF-1α信号通路在骨形态发生蛋白2（BMP-2）诱导的根尖乳头干细胞（SCAP）牙向分化中的作用。在培养的SCAP中检测到CXCR 4的表达，并且在Transwell实验中SDF-1α促进SCAP的迁移。通过siRNA阻断SDF-1α信号传导显著影响BMP-2诱导的矿化结节形成和碱性磷酸酶（ALP）活性。此外，阻断SDF-1α信号通路可抑制BMP-2诱导的Runx-2的早期表达，并强烈抑制BMP-2诱导的牙本质基质蛋白1（DNF-1）和牙本质涎磷蛋白（DSPP）的表达。此外，SDF-1α和BMP-2信号之间的相互作用通过细胞内Smads和Erk活化介导。结论：SDF-1α能显著促进SCAP细胞的迁移。此外，我们还揭示了SDF-1α/CXCR 4信号通路在BMP-2诱导的SCAP牙源性分化中的共同作用，这些发现可能为牙髓再生的新策略提供依据。
Stromal-derived factor-1α (SDF-1α) is a chemokine signaling molecule that binds to the transmembrane receptor CXC chemokine receptor-4 (CXCR4) and carries out important functions in development tissue homeostasis. SDF-1α signaling via CXCR4 regulates the recruitment of stem and precursor cells to support tissue-specific repair or regeneration. In this study, we examined the contribution of SDF-1α signaling to the odontogenic differentiation of stem cells from the apical papilla (SCAP) induced by bone morphogenic protein 2 (BMP-2). CXCR4 expression was detected in cultured SCAP and SDF-1α promoted the migration of SCAP in Transwell assays. Blocking SDF-1α signaling by treatment with siRNA significantly affected BMP-2-induced mineralized nodule formation and alkaline phosphatase (ALP) activity. Moreover, blocking SDF-1α signaling inhibited the BMP-2-induced early expression of runt-related factor-2 (Runx-2) and strongly suppressed the induction of dentin matrix protein 1 (DMP-1) and dentin sialophosphoprotein (DSPP) expression by BMP-2. Furthermore, the interaction between SDF-1α and BMP-2 signaling was mediated via intracellular Smads and Erk activation. In conclusion, our results demonstrated that SDF-1α can significantly promote the migration of SCAP. Moreover, we revealed corequirement of the SDF-1α/CXCR4 signaling pathways in the BMP-2-induced odontogenic differentiation of SCAP, and these findings may be applied in new strategies for dental pulp regeneration.