An Inhibitory Role of Osthole in Rat MSCs Osteogenic Differentiation and Proliferation via Wnt/β-Catenin and Erk1/2-MAPK Pathways
An Inhibitory Role of Osthole in Rat MSCs Osteogenic Differentiation and Proliferation via Wnt/β-Catenin and Erk1/2-MAPK Pathways
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蛇床子素通过 Wnt/β-Catenin 和 Erk1/2-MAPK 通路对大鼠 MSC 成骨分化和增殖的抑制作用
DOI：
10.1159/000445590
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发表时间：
2016-01-01
影响因子：
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通讯作者：
Ding, Daofang
中科院分区：
文献类型：
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作者：
Hu, Hongyang;Chen, Min;Ding, Daofang
目的：骨髓间充质干细胞（MSCs）负责成年期新骨形成。越来越多的证据表明蛇床子素促进原代成骨细胞的成骨分化。本研究旨在探讨蛇床子素是否具有促进骨髓间充质干细胞成骨分化的作用及其机制。方法：用梯度浓度的蛇床子素（6.25 μ M、12.5 μ M和25 μ M）处理MSC。用增殖细胞核抗原（PCNA）和细胞周期蛋白D1抗体，荧光激活细胞分选（FACS）和细胞计数试剂盒8（CCK 8）的蛋白质印迹法评估细胞增殖。将MSC在成骨诱导培养基中培养1或2周。碱性磷酸酶（ALP）染色、茜素红染色、钙离子内流和定量PCR（qPCR）检测MSCs的成骨分化。通过Wnt/beta-catenin、PI 3 K/Akt、BMPs/smad 1/5/8和MAPK信号通路中的抗体进行蛋白质印迹，进一步评估了Osthole诱导成骨的潜在机制。结果：蛇床子素对大鼠骨髓间充质干细胞的增殖有抑制作用，且呈剂量依赖性。蛇床子素通过下调Wnt/beta-catenin和Erk 1/2-MAPK信号通路抑制大鼠MSCs的成骨分化。结论：蛇床子素抑制大鼠骨髓间充质干细胞增殖和成骨分化，其机制可能与阻断Wnt/beta-catenin和Frk 1/2-MAPK信号通路有关。(C)2016作者（s）由S. Karger AG，巴塞尔
Elockground/Aims: Bone marrow-derived mesenchymal stem cells (MSCs) are responsible for new bone formation during adulthood. Accumulating evidences showed that Osthole promotes the osteogenic differentiation in primary osteoblasts. The aim of this study was to investigate whether Osthole exhibits a potential to stimulate the osteogenic differentiation of MSCs and the underlying mechanism. Methods: MSCs were treated with a gradient concentration of Osthole (6.25 mu M, 12.5 mu M, and 25 mu M). Cell proliferation was assessed by western blotting with the proliferating cell nuclear antigen (PCNA) and Cyclin D1 antibodies, fluorescence activated cell sorting (FACS), and cell counting kit 8 (CCK8). MSCs were cultured in osteogenesis-induced medium for one or two weeks. The osteogenic differentiation of MSCs was estimated by Alkaline Phosphatase (ALP) staining, Alizarin red staining, Calcium influx, and quantitative PCR (qPCR). The underlying mechanism of Osthole-induced osteogenesis was further evaluated by western blotting with antibodies in Wnt/beta-catenin, PI3K/Akt, BMPs/smad1/5/8, and MAPK signaling pathways. Results: Osthole inhibited proliferation of rat MSCs in a dose-dependent manner. Osthole suppressed osteogenic differentiation of rat MSCs by down-regulating the activities of Wnt/beta-catenin and Erk1/2-MAPK signaling. Conclusions: Osthole inhibits the proliferation and osteogenic differentiation of rat MSCs, which might be mediated through blocking the Wnt/beta-catenin and Frk1/2-MAPK signaling pathways. (C) 2016 The Author(s) Published by S. Karger AG, Basel