William G. Lowrie Department of Chemical and Biomolecular Engineering, Ohio State University, Columbus, OH, USA.
Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL, USA.
J Tissue Eng Regen Med. 2017 Jan;11(1):276-284. doi: 10.1002/term.1911. Epub 2014 Jun 11.
Human amniotic fluid-derived stem cells (hAFSCs) are a novel cell source for generating osteogenic cells to treat bone diseases. Effective induction of osteogenic differentiation from hAFSCs is critical to fulfil their therapeutic potential. In this study, naringin, the main active compound of Rhizoma drynariae (a Chinese herbal medicine), was used to stimulate the proliferation and osteogenic differentiation of hAFSCs. The results showed that naringin enhanced the proliferation and alkaline phosphatase activity (ALP) of hAFSCs in a dose-dependent manner in the range 1-100 µg/ml, while an inhibition effect was observed at 200 µg/ml. Consistently, the calcium content also increased with naringin concentration up to 100 µg/ml. The enhanced osteogenic differentiation of hAFSCs by naringin was further confirmed by the dose-dependent upregulation of marker genes, including osteopontin (OPN) and Collagen I from RT-PCR analysis. The increased osteoprotegerin (OPG) expression and minimal expression of receptor activator of nuclear factor-κB ligand (RANKL) suggested that naringin also inhibited osteoclastogenesis of hAFSCs. In addition, the gene expressions of bone morphogenetic protein 4 (BMP4), runt-related transcription factor 2 (RUNX2), β-catenin and Cyclin D1 also increased significantly, indicating that naringin promotes the osteogenesis of hAFSCs via the BMP and Wnt-β-catenin signalling pathways. These results suggested that naringin can be used to upregulate the osteogenic differentiation of hAFSCs, which could provide an attractive and promising treatment for bone disorders. Copyright © 2014 John Wiley & Sons, Ltd.
人羊膜间充质干细胞（hAFSCs）是一种新型的细胞来源，可用于产生成骨细胞来治疗骨疾病。有效地诱导 hAFSCs 向成骨细胞分化对于发挥其治疗潜力至关重要。在这项研究中，柚皮苷，一种中药虎杖的主要活性化合物，被用于刺激 hAFSCs 的增殖和成骨分化。结果表明，柚皮苷在 1-100μg/ml 的范围内以剂量依赖的方式增强了 hAFSCs 的增殖和碱性磷酸酶活性（ALP），而在 200μg/ml 时观察到抑制作用。一致地，钙含量也随着柚皮苷浓度的增加而增加，最高可达 100μg/ml。通过 RT-PCR 分析，柚皮苷对标记基因，包括骨桥蛋白（OPN）和 I 型胶原的剂量依赖性上调，进一步证实了 hAFSCs 的成骨分化增强。骨保护素（OPG）表达的增加和核因子-κB 受体激活剂配体（RANKL）的最小表达表明，柚皮苷还抑制了 hAFSCs 的破骨细胞生成。此外，骨形态发生蛋白 4（BMP4）、 runt 相关转录因子 2（RUNX2）、β-连环蛋白和细胞周期蛋白 D1 的基因表达也显著增加，表明柚皮苷通过 BMP 和 Wnt-β-连环蛋白信号通路促进 hAFSCs 的成骨作用。这些结果表明，柚皮苷可用于上调 hAFSCs 的成骨分化，为骨疾病的治疗提供了一种有吸引力和有前途的方法。版权所有©2014 约翰威立父子公司
