Yu Guo-Yong, Zheng Gui-Zhou, Chang Bo, Hu Qin-Xiao, Lin Fei-Xiang, Liu De-Zhong, Wu Chu-Cheng, Du Shi-Xin, Li Xue-Dong
Department of Orthopedics, The First Affiliated Hospital, Shantou University Medical College, 57 Changping Road, Shantou, Guangdong Province 515041, China.
Department of Orthopedics, The First Affiliated Hospital, Shantou University Medical College, 57 Changping Road, Shantou, Guangdong Province 515041, China; Department of Orthopedics, The Affiliated Luohu Hospital of Shenzhen University, Shenzhen, Guangdong Province 518000, China.
Stem Cells Int. 2016;2016:7130653. doi: 10.1155/2016/7130653. Epub 2016 Mar 16.
Naringin is a major flavonoid found in grapefruit and is an active compound extracted from the Chinese herbal medicine Rhizoma Drynariae. Naringin is a potent stimulator of osteogenic differentiation and has potential application in preventing bone loss. However, the signaling pathway underlying its osteogenic effect remains unclear. We hypothesized that the osteogenic activity of naringin involves the Notch signaling pathway. Rat bone marrow stromal cells (BMSCs) were cultured in osteogenic medium containing-naringin, with or without DAPT (an inhibitor of Notch signaling), the effects on ALP activity, calcium deposits, osteogenic genes (ALP, BSP, and cbfa1), adipogenic maker gene PPARγ2 levels, and Notch expression were examined. We found that naringin dose-dependently increased ALP activity and Alizarin red S staining, and treatment at the optimal concentration (50 μg/mL) increased mRNA levels of osteogenic genes and Notch1 expression, while decreasing PPARγ2 mRNA levels. Furthermore, treatment with DAPT partly reversed effects of naringin on BMSCs, as judged by decreases in naringin-induced ALP activity, calcium deposits, and osteogenic genes expression, as well as upregulation of PPARγ2 mRNA levels. These results suggest that the osteogenic effect of naringin partly involves the Notch signaling pathway.
柚皮苷是葡萄柚中发现的一种主要黄酮类化合物，也是从中药骨碎补中提取的一种活性化合物。柚皮苷是成骨分化的有效刺激剂，在预防骨质流失方面具有潜在应用价值。然而，其成骨作用的信号通路仍不清楚。我们推测柚皮苷的成骨活性涉及Notch信号通路。将大鼠骨髓间充质干细胞（BMSCs）培养在含有柚皮苷的成骨培养基中，添加或不添加DAPT（一种Notch信号抑制剂），检测其对碱性磷酸酶（ALP）活性、钙沉积、成骨基因（ALP、骨涎蛋白（BSP）和核心结合因子α1（cbfa1））、脂肪生成标记基因PPARγ2水平以及Notch表达的影响。我们发现柚皮苷剂量依赖性地增加ALP活性和茜素红S染色，在最佳浓度（50μg/mL）处理可增加成骨基因的mRNA水平和Notch1表达，同时降低PPARγ2 mRNA水平。此外，用DAPT处理部分逆转了柚皮苷对BMSCs的作用，表现为柚皮苷诱导的ALP活性、钙沉积和成骨基因表达降低，以及PPARγ2 mRNA水平上调。这些结果表明，柚皮苷的成骨作用部分涉及Notch信号通路。
