Hwang Jeong-Ha, Cha Pu-Hyeon, Han Gyoonhee, Bach Tran The, Min Do Sik, Choi Kang-Yell
1] Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea [2] Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Institute of Ecology and Biological Resources, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam.
Exp Mol Med. 2015 Mar 20;47(3):e152. doi: 10.1038/emm.2014.115.
The Wnt/β-catenin pathway has a role in osteoblast differentiation and bone formation. We screened 100 plant extracts and identified an extract from Euodia sutchuenensis Dode (ESD) leaf and young branch as an effective activator of the Wnt/β-catenin pathway. ESD extract increased β-catenin levels and β-catenin nuclear accumulation in murine primary osteoblasts. The ESD extract also increased mRNA levels of osteoblast markers, including RUNX2, BMP2 and COL1A1, and enhanced alkaline phosphatase (ALP) activity in murine primary osteoblasts. Both ESD extract-induced β-catenin increment and ALP activation were abolished by β-catenin knockdown, confirming that the Wnt/β-catenin pathway functions in osteoblast differentiation. ESD extract enhanced terminal osteoblast differentiation as shown by staining with Alizarin Red S and significantly increased murine calvarial bone thickness. This study shows that ESD extract stimulates osteoblast differentiation via the Wnt/β-catenin pathway and enhances murine calvarial bone formation ex vivo.
Wnt/β-连环蛋白信号通路在成骨细胞分化和骨形成过程中发挥作用。我们筛选了100种植物提取物,鉴定出一种来自川鄂吴茱萸(ESD)叶和嫩枝的提取物是Wnt/β-连环蛋白信号通路的有效激活剂。ESD提取物可增加小鼠原代成骨细胞中β-连环蛋白的水平及其在细胞核中的积累。ESD提取物还可提高包括RUNX2、BMP2和COL1A1在内的成骨细胞标志物的mRNA水平,并增强小鼠原代成骨细胞中的碱性磷酸酶(ALP)活性。β-连环蛋白基因敲低消除了ESD提取物诱导的β-连环蛋白增加和ALP激活,证实Wnt/β-连环蛋白信号通路在成骨细胞分化中发挥作用。如茜素红S染色所示,ESD提取物增强了终末成骨细胞分化,并显著增加了小鼠颅骨厚度。本研究表明,ESD提取物通过Wnt/β-连环蛋白信号通路刺激成骨细胞分化,并在体外增强小鼠颅骨的骨形成。