miR-136在去势小鼠颌骨骨细胞雌激素信号响应过程中的作用及其机制研究

项目名称： miR-136在去势小鼠颌骨骨细胞雌激素信号响应过程中的作用及其机制研究

项目编号： No.81470716

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 吴珺华

作者单位： 同济大学

项目金额： 73万元

中文摘要： 颌骨骨丢失与雌激素水平失衡诱导的骨质疏松相关，其骨丢失程度较长骨更明显。骨细胞雌激素信号响应在颌骨骨吸收和骨稳态中发挥重要作用，是一个新兴的研究热点。我们前期研究在去势小鼠颌骨骨组织中筛选并鉴定了miR-136是骨细胞雌激素信号响应中的重要因子。并且预实验初步发现miR-136促进了骨细胞的自噬和凋亡行为，并提高了细胞胞间通讯效率。本项目拟在骨细胞样MLO-Y4细胞和去势小鼠两个层面深入研究miR-136参与的信号通路及其作用靶点，探明其调节骨细胞雌激素响应行为的作用机制，明确miR-136调控骨稳态的功能，并尝试在去势小鼠颌骨组织中干预miR-136的表达，探讨其作为颌骨骨质疏松治疗靶点的可行性。本研究的开展将会为颌骨骨质疏松生物学标记物以及靶向治疗提供新的思路和理论依据。

中文关键词： 骨质疏松；信号通路；微小RNA；雌激素

英文摘要： The bone loss of jaw bone is related to osteoporosis induced by imbalanced estrogen levels, which is more obvious than that of long bone. The response of the osteocyte to estrogen plays an important role in jaw bone absorption and maintenance, presenting an emerging research field. After previous screening, we identified miR-136 as an important factor in ovariectomized mice jaw bone osteocyte's response to estrogen. Besides, we found miR-136 could promote autophagy and apoptosis of osteocyte, and improve efficiency of intercellular communication. This project intends to study the signaling pathways that miR-136 involved and its targets in osteocyte-like MLO-Y4 cells and ovariectomized mice, respectively. By this method, we could ascertain the regulation mechanism of miR-136 in osteocyte's response to estrogen, clearing its action in bone homeostasis. In addition, interference on miR-136 expression of ovariectomized mice jaw bone could explore its feasibility as therapeutic target of mandibular osteoporosis. This study will provide new ideas and theoretical basis for biological markers and targeted therapy of mandibular osteoporosis.

英文关键词： oeteoporosis;signalling channel;microRNA;estrogen