基于Aptamer-Tieg1靶向作用于成骨前体细胞促进骨形成的策略研究

The metabolic activity of bone in osteoporosis is compromised by an imbalance between the rate of bone resorption by activated osteoclasts and replenishment of lost bone by activity of the osteoblastic bone forming. Preosteoblasts targeted approach aimed at promoting osteoblastic bone formation may hold therapeutic potential. However, a major bottleneck is the lack of safe, convenient and efficiency osteogenic transcription regulator delivery systems. Our previous research has identified the aptamer with specific affinity to Bone marrow mesenchymal stem cells (BMSCs). On the basis of our previous research, we propose a new therapeutic strategy of attaching Tieg1 to aptamer to target preosteoblasts, so that TIEG1 enhance Osx expression thus to induce osteogenesis. We select the preosteoblasts-specific aptamer, synthetize the Aptamer-Tieg1 compound, then, intervene preosteoblasts in vitro and the osteoporotic mice models in vivo. So we can find out if preosteoblasts can be targeted, and observe the tissue-specific distribution of Aptamer-Tieg1, differentiation and metabolism of preosteoblasts. Thus we can provide a new strategy for treatment of osteoporosis.

成骨细胞介导的骨形成和破骨细胞介导的骨吸收活动失衡导致骨质疏松症（osteoporosis , OP）。通过靶向诱导成骨前体细胞分化从而促进成骨是一种理论上有效的治疗策略，然而如何构建安全便捷有效的成骨前体细胞特异性转录调控因子投递系统成为研究的关键。本课题在前期鉴定出成骨性细胞分化潜能的骨髓间充质干细胞特异性结合核酸适配体（Aptamer）的基础上，拟筛选出成骨前体细胞特异性Aptamer，进而合成Aptamer-Tieg1复合物，基于Tieg1促进成骨细胞特异性转录因子Osterix表达的作用，用Aptamer-Tieg1干预成骨前体细胞，观察其对锚定的成骨前体细胞分化的影响；用Aptamer-Tieg1干预OP小鼠模型，观察其在体内组织分布状况，检测成骨前体细胞分化及骨代谢状况，确定成骨前体细胞是否能被锚定并分化为成骨细胞，促进骨形成，为临床OP治疗提供新策略。

成骨细胞介导的骨形成和破骨细胞介导的骨吸收活动失衡导致骨质疏松症（osteoporosis , OP）。通过靶向诱导成骨前体细胞分化从而促进成骨是一种理论上有效的治疗策略，然而如何构建安全便捷有效的成骨前体细胞特异性转录调控因子投递系统成为研究的关键。本课题在前期鉴定出成骨性细胞分化潜能的骨髓间充质干细胞特异性结合核酸适配体（Aptamer）的基础上，拟筛选出成骨前体细胞特异性Aptamer，进而合成Aptamer-Tieg1复合物，基于Tieg1促进成骨细胞特异性转录因子Osterix表达的作用，用Aptamer-Tieg1干预成骨前体细胞，观察其对锚定的成骨前体细胞分化的影响；用Aptamer-Tieg1干预OP小鼠模型，观察其在体内组织分布状况，检测成骨前体细胞分化骨代谢状况，确定成骨前体细胞是否能被锚定并分化为成骨细胞，促进骨形成，为临床OP治疗提供新策略。