Emodin promotes the osteogenesis of MC3T3-E1 cells via BMP-9/Smad pathway and exerts a preventive effect in ovariectomized rats
Emodin promotes the osteogenesis of MC3T3-E1 cells via BMP-9/Smad pathway and exerts a preventive effect in ovariectomized rats
复制标题
DOI：
10.1093/abbs/gmx087
复制
发表时间：
2017-10-01
影响因子：
3.7
通讯作者：
Gao, Yanhong
中科院分区：
文献类型：
--
作者：
Chen, Xiaojing;Zhang, Shuang;Gao, Yanhong
大黄素是从中药大黄和虎杖中提取的一种天然蒽醌类化合物，据报道具有促进成骨细胞分化的作用。然而，其调节成骨能力的机制尚不清楚。本研究的目的是确定大黄素在体外成骨细胞功能中的作用及其在体内的骨保护作用。大黄素促进MC 3 T3-E1细胞的分化和矿化，表现为碱性磷酸酶活性升高和矿化结节数量增加。在培养的成骨细胞中，大黄素显著诱导BMP-9的mRNA表达，BMP-9是研究最少但最成骨的骨形态发生蛋白（BMP）之一。此外，骨形态发生蛋白受体-Smad（BMPR-Smad）信号轴和p38丝裂原活化蛋白激酶（p38 MAPK）被激活。通过评价骨组织形态学、骨小梁微结构、骨骼力学性能和卵巢切除（OVX）大鼠骨转换的血清参数来评价大黄素的体内功能。大黄素联合小剂量雌激素与单独小剂量雌激素相比，改善了第四腰椎骨小梁微结构，增强了椎体强度。此外，大黄素抑制卵巢切除引起的血清骨钙素（OC）的升高。此外，联合治疗对子宫肥大的副作用比单独使用大剂量雌激素少。然而，大黄素单独没有发挥任何骨保护作用。这些结果表明，大黄素可能是一个很有前途的替代剂骨质疏松症的联合治疗。
Emodin, a natural anthraquinone extracted from the Chinese herbs rhubarb and giant knotweed rhizome, has been reported to enhance osteoblast differentiation. However, the mechanisms underlying its ability to regulate osteogenesis are unclear. The objective of this study was to determine the role of emodin in osteoblast function in vitro and its osteoprotective effect in vivo. Emodin enhanced the differentiation and mineralization of MC3T3-E1 cells, as evidenced by elevated alkaline phosphatase activity and increased number of mineralized nodules. In cultured osteoblasts, emodin significantly induced the mRNA expression of BMP-9 which is one of the least studied but most osteogenic bone morphogenetic proteins (BMPs). Furthermore, the bone morphogenetic protein receptor-Smad (BMPR-Smad) signaling axis and p38 mitogen activated protein kinase (p38 MAPK) were activated. The in vivo function of emodin were evaluated by assessing bone histomorphology, trabecular bone microarchitecture, mechanical properties of the skeleton, and serum parameters of bone turnover in ovariectomized (OVX) rats. Emodin combined with low-dose of estrogen improved trabecular bone microarchitecture in the fourth lumbar vertebra compared with low-dose estrogen alone and enhanced vertebral body strength. Moreover, emodin suppressed the OVX-induced elevation of serum osteocalcin (OC). In addition, there were fewer side effects on uterine hypertrophy with the combination therapy than with high-dose estrogen alone. However, emodin alone did not exert any osteoprotective effect. These results suggest that emodin may be a promising alternative agent for osteoporosis in combination therapy.