School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, 1168 West Chunrong Road, Kunming, Yunnan 650500, China; Department of Pharmacy, The Second Affiliated Hospital of Kunming Medical University, 374 Dianmian Avenue, Kunming, Yunnan 650101, China.
School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, 1168 West Chunrong Road, Kunming, Yunnan 650500, China.
Biomed Pharmacother. 2018 Mar;99:319-324. doi: 10.1016/j.biopha.2018.01.040.
Geraniin is an ellagitannin isolated from Phyllanthus amarus and has a wide range of bioactivities. Our previous study demonstrated that geraniin could alleviate osteoporosis by accelerating bone formation, but the mechanism remains unclear. This study aimed to elucidate the molecular mechanisms by which geraniin promotes osteoblast proliferation and differentiation in vitro. Primary rat bone marrow-derived mesenchymal stem cells were separated and divided into sham operated (Sham) group, Sham treated with geraniin (Sham + GE) group, ovariectomized (OVX) group, OVX treated with geraniin (OVX + GE) group, OVX treated with osteogenic medium (OVX + OM) group, OVX treated with Wnt inhibitor (OVX + WI) group, and OVX treated with Wnt inhibitor and geraniin (OVX + W I + GE) group. Following bilateral ovariectomy, the expression of β-catenin, frizzled2, LRP6, TCF4, LEF1, c-myc, cyclin D1, Runx2 and osterix significantly reduced, while the expression of axin2 significantly increased (P < 0.05). Geraniin enhanced the expression of β-catenin, frizzled2, LRP6, TCF4, LEF1, c-myc, cyclin D1, Runx2 and osterix, while inhibited the expression of axin2 (P < 0.05). Wnt inhibitor significantly weakened geraniin-induced Wnt/β-catenin activation (P < 0.05). In conclusion, geraniin enhances the activation of Wnt/β-catenin pathway, which may explain how it promotes osteoblast proliferation and differentiation.
没食子酸乙酯是从叶下珠中分离得到的鞣花单宁，具有广泛的生物活性。我们之前的研究表明，没食子酸乙酯通过加速骨形成来缓解骨质疏松症，但机制尚不清楚。本研究旨在阐明没食子酸乙酯在体外促进成骨细胞增殖和分化的分子机制。分离并培养原代大鼠骨髓间充质干细胞，分为假手术（Sham）组、Sham 加没食子酸乙酯（Sham+GE）组、去卵巢（OVX）组、OVX 加没食子酸乙酯（OVX+GE）组、OVX 加成骨培养基（OVX+OM）组、OVX 加 Wnt 抑制剂（OVX+WI）组和 OVX 加 Wnt 抑制剂和没食子酸乙酯（OVX+W I+GE）组。双侧卵巢切除后，β-catenin、frizzled2、LRP6、TCF4、LEF1、c-myc、cyclin D1、Runx2 和osterix 的表达显著降低，而 axin2 的表达显著增加（P<0.05）。没食子酸乙酯增强了β-catenin、frizzled2、LRP6、TCF4、LEF1、c-myc、cyclin D1、Runx2 和osterix 的表达，同时抑制了 axin2 的表达（P<0.05）。Wnt 抑制剂显著减弱了没食子酸乙酯诱导的 Wnt/β-catenin 激活（P<0.05）。综上所述，没食子酸乙酯增强了 Wnt/β-catenin 通路的激活，这可能解释了它如何促进成骨细胞的增殖和分化。
