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碱性成纤维细胞生长因子通过成纤维细胞生长因子受体和 PLCγ 信号通路抑制人牙髓干细胞矿化但诱导其神经元分化。

Basic fibroblast growth factor inhibits mineralization but induces neuronal differentiation by human dental pulp stem cells through a FGFR and PLCγ signaling pathway.

机构信息

Developing Research Unit of Genetic and Anatomical Analyses of Craniofacial Structures, Chulalongkorn University, Bangkok 10330, Thailand.

出版信息

J Cell Biochem. 2011 Jul;112(7):1807-16. doi: 10.1002/jcb.23097.

Abstract

Basic fibroblast growth factor (basic FGF) has pivotal roles in the function of various cell types. Here, we report the effects of basic FGF in the regulation of dental pulp stem cell (DPSC) behaviors including maintaining stemness and directing differentiation. Cells isolated from human dental pulp tissues exhibited stem cell properties including the expression of mRNA markers for embryonic and mesenchymal stem cells, the expression of Stro-1, and the multipotential differentiation. Basic FGF stimulated colony-forming units of DPSCs and up-regulated the expression of the embryonic stem cell markers; Oct4, Rex-1, and Nanog. Moreover, osteogenic medium containing basic FGF inhibited alkaline phosphatase enzymatic activity and mineralization of DPSCs. On the contrary, basic FGF appeared to be an influential growth factor in the neurogenic differentiation of DPSCs. In the presence of basic FGF, increased DPSCs neurosphere size and the up-regulation of neurogenic markers were noted. Inhibitors of FGFR or PLCγ were able to ablate the basic FGF-induced neuronal differentiation of DPSCs. Taken together, these results suggest basic FGF may be involved in the mechanisms controlling DPSCs cell fate decisions.

摘要

碱性成纤维细胞生长因子(basic FGF)在各种细胞类型的功能中起着关键作用。在这里,我们报告碱性成纤维细胞生长因子在调节牙髓干细胞(DPSC)行为中的作用,包括维持干细胞特性和指导分化。从人牙髓组织中分离的细胞表现出干细胞特性,包括胚胎和间充质干细胞的 mRNA 标志物的表达、Stro-1 的表达和多能分化。碱性成纤维细胞刺激牙髓干细胞集落形成单位并上调胚胎干细胞标志物的表达;Oct4、Rex-1 和 Nanog。此外,含有碱性成纤维细胞生长因子的成骨培养基抑制碱性磷酸酶酶活性和 DPSCs 的矿化。相反,碱性成纤维细胞似乎是 DPSCs 神经发生分化的有影响力的生长因子。在碱性成纤维细胞存在的情况下,注意到 DPSCs 神经球大小增加和神经发生标记物的上调。FGFR 或 PLCγ 的抑制剂能够消除碱性成纤维细胞诱导的 DPSCs 的神经元分化。总之,这些结果表明碱性成纤维细胞可能参与控制 DPSCs 细胞命运决定的机制。

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