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无机多聚磷酸盐通过激活 Wnt/β-连环蛋白信号通路提高纳米纤维结构上培养的间充质干细胞的成骨分化潜能。

Increased osteogenic differentiation potential of MSCs cultured on nanofibrous structure through activation of Wnt/β-catenin signalling by inorganic polyphosphate.

机构信息

a Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine , Shahid Beheshti University of Medical Sciences , Tehran , Iran.

b Department of Biotechnology, School of Advanced Technologies in Medicine , Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences , Tehran , Iran.

出版信息

Artif Cells Nanomed Biotechnol. 2018;46(sup3):S943-S949. doi: 10.1080/21691401.2018.1521816. Epub 2018 Nov 29.

DOI:10.1080/21691401.2018.1521816
PMID:30489168
Abstract

There are several signal pathways involved in bone regeneration that can be triggered by several factors including mechanical, physical and chemical factors. Chemical growth factors are commonly used in differentiation induction to stem cells, while have side effects. In this study, inorganic poly-phosphate (poly-P) as a natural-based molecule was used to induce Wnt/β-catenin signalling in adipose-derived mesenchymal stem cells (AT-MSCs) while cultured on 2D and 3D culture systems. Common osteogenic markers were investigated to detect the influence of Wnt/β-catenin signalling induction on osteogenic differentiation of AT-MSCs and signalling genes up regulation was also evaluated by its related gene expression measurement. Results were shown that Cyclin-D1 and β-catenin gene expression was significantly increased in those cells treated by poly-P. Osteogenic differentiation of those stem cells with higher Cyclin-D1 and β-catenin gene expression was significantly higher than other groups except those stem cells cultured under osteogenic medium. According to the results, inorganic poly-P can trigger osteogenic differentiation in stem cells through Wnt/β-catenin signalling and this potential is almost close to common osteogenic growth factors and this could be used as natural-based molecules in bone regeneration, apart from concerns about the use of chemical factors.

摘要

有几种信号通路参与骨再生,这些信号通路可以被多种因素触发,包括机械、物理和化学因素。化学生长因子通常用于诱导干细胞的分化,但其存在副作用。在这项研究中,无机多磷酸盐(poly-P)作为一种天然分子,被用于在 2D 和 3D 培养系统中诱导脂肪间充质干细胞(AT-MSCs)中的 Wnt/β-catenin 信号通路。研究了常见的成骨标志物,以检测 Wnt/β-catenin 信号通路诱导对 AT-MSCs 成骨分化的影响,并通过相关基因表达测量评估信号基因的上调。结果表明,用 poly-P 处理的细胞中 Cyclin-D1 和 β-catenin 基因的表达显著增加。这些具有较高 Cyclin-D1 和 β-catenin 基因表达的干细胞的成骨分化明显高于其他组,除了那些在成骨培养基中培养的干细胞。根据这些结果,无机多磷酸盐可以通过 Wnt/β-catenin 信号通路触发干细胞的成骨分化,其潜力几乎接近常见的成骨生长因子,并且可以作为天然分子用于骨再生,而不必担心使用化学因子。

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