miR-181b调控成骨细胞功能的分子机制及在骨质疏松治疗中的作用研究

骨质疏松症是严重威胁中老年人健康的重大医学问题，其发病的分子机制和高效药物尚需进一步的研究。课题组前期研究发现miR-181b在低骨密度样本中表达显著上调。预实验发现过表达miR-181b可引起成骨细胞相关基因表达下调，成骨细胞分化能力减弱、矿化能力减弱。上述证据提示miR-181b调控成骨细胞功能，并在骨质疏松病理过程中发挥重要作用。本项目拟构建miR-181b成骨细胞特异性敲除小鼠和过表达小鼠模型，综合运用细胞生物学和分子生物学手段，在小鼠体内和体外研究miR-181b对成骨细胞功能的调节作用，并深入探讨其分子机制，进而利用去卵巢骨质疏松模型研究miR-181b抑制剂对骨质疏松小鼠的治疗作用。 本研究可进一步阐明和理解骨质疏松症的分子致病机理，为骨质疏松症核酸药物治疗提供理论依据。

Osteoporosis is a major medical problem that threatens the health of the elderly, but further study is needed to understand its molucular mechanism and efficient treatment. Our pilot study showed that overexpression of miR-181b reduced the mRNA expression of some target genes on osteoblast, Alp activity and mineral deposition. These findings suggest that miR-181b regulates osteoblast function and plays an important role in pathogenesis of osteoporosis. In the present project, we intend to construct osteoblast-specific miR-181b knockout mice and transgenic mice and use methods of cell biology and molecular biology to investigate the regulating funtion of miR-181b in osteoblast,and further to explore the molecular mechanism of miR-181b. Finally, we will determine the therapeutic effects of intravenous administration of miR-181b inhibitor on ovariectomy-induced osteoporosis mouse model. This study is significant and promising for our understanding on the molecular mechanism underlying osteoporosis and for identifying targets for development of novel therapeutic agents and approaches for osteoporosis.