Cheng Xun, Wei Biaofang, Sun Lijuan, Hu Xiaofang, Liang Jichao, Chen Yong
Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Collaborative Innovation Center for Green Transformation of Bio-Resources, Hubei University, Wuhan, 430062, China.
Department of Orthopaedic, Linyi People's Hospital, Science and Technology Develop Project of Shandong province, Linyi, 276000, China.
Phytother Res. 2016 Oct;30(10):1680-1688. doi: 10.1002/ptr.5674. Epub 2016 Jul 10.
Astragaloside I (As-I), one of the main active ingredients in Astragalus membranaceus, is believed to have osteogenic properties, but this hypothesis has not been investigated in detail. In the present work, the As-I-induced osteogenic effects and its underlying mechanism were studied in MC3T3-E1 cells. The results indicated that the cellular levels of ALP and extracellular matrix calcium increased in a dose-dependent manner by As-I. To clarify the mechanisms involved in this process, the effect of As-I on the key osteogenic-related genes was investigated. We found that As-I stimulated the expression of β-catenin and Runx2 in MC3T3-E1 cells, which play central roles in the Wnt/β-catenin signaling pathway, suggesting that As-I could promote osteoblastic differentiation by regulating the Wnt/β-catenin signaling pathway. Moreover, the osteogenic effect of As-I could be inhibited by DKK-1, which is the classical inhibitor of Wnt/β-catenin-signaling pathway. Furthermore, As-I also increased BMP-2, BGP and OPG/RANKL expression, which are also activated by Wnt/β-catenin signaling pathway. Taken together, our findings show that As-I stimulates osteoblast differentiation through the Wnt/β-catenin signaling pathway, which also activates the BMP pathway and RANK pathway, thus highlighting the As-I for pharmaceutical and medicinal applications such as treating bone disease. Copyright © 2016 John Wiley & Sons, Ltd.
黄芪甲苷I（As-I）是黄芪的主要活性成分之一，被认为具有成骨特性，但这一假说尚未得到详细研究。在本研究中，我们在MC3T3-E1细胞中研究了As-I诱导的成骨作用及其潜在机制。结果表明，As-I可使碱性磷酸酶（ALP）的细胞水平和细胞外基质钙呈剂量依赖性增加。为阐明这一过程涉及的机制，我们研究了As-I对关键成骨相关基因的影响。我们发现，As-I可刺激MC3T3-E1细胞中β-连环蛋白和Runx2的表达，它们在Wnt/β-连环蛋白信号通路中起核心作用，这表明As-I可能通过调节Wnt/β-连环蛋白信号通路促进成骨细胞分化。此外，As-I的成骨作用可被DKK-1抑制，DKK-1是Wnt/β-连环蛋白信号通路的经典抑制剂。此外，As-I还增加了骨形态发生蛋白-2（BMP-2）、骨钙素（BGP）和骨保护素/核因子κB受体活化因子配体（OPG/RANKL）的表达，这些也可被Wnt/β-连环蛋白信号通路激活。综上所述，我们的研究结果表明，As-I通过Wnt/β-连环蛋白信号通路刺激成骨细胞分化，并激活BMP通路和RANK通路，从而突出了As-I在治疗骨疾病等药物和医学应用方面的价值。版权所有© 2016约翰威立父子有限公司。
