颌面部骨缺损严重影响患者身心健康，常用自体骨移植修复但有其局限，采用骨组织工程方法为现研究热点，但如何安全高效定向诱导种子细胞成骨分化是一核心问题，多采用在骨缺损局部释放促成骨相关因子或通过基因转染等方法但存在一些问题。最新文献报道lncRNAs可以明显地调控间充质干细胞的成骨分化，并通常与miRNAs交互协调发挥作用，有望成为新的突破点。课题组前期研究也证实人脂肪干细胞成骨分化过程相关lncRNAs表达明显上调或下调，但尚未见其交互作用调控人脂肪干细胞成骨分化的报道。本项目拟通过基因芯片筛选、系列实验确认、体外及体内验证、深入探索机制的技术路线确定在人脂肪干细胞成骨分化中调控作用最佳的lncRNAs，研究并鉴定与之交互作用的miRNAs，明确配对的lncRNAs-miRNAs调控脂肪干细胞成骨分化的机制，并研究该交互作用与成骨分化的重要信号通路产生作用的分子靶点，为骨缺损修复提供新思路。

Maxillofacial bone defects severely impact patients’physical and mental health, and the common therapeutic method of bone defects repair is autogenous bone graft which has limitations. Therefore, bone tissue engineering has become a hot topic and one of the key points is to induce osteogenic differentiation of seed cells safely and efficiently. Most studies employed releasing osteogenic factors in bone defects or conducting gene transduction, but there are some limitations. Recent studies found that specific long noncoding RNAs (lncRNAs) regulated osteogenic differentiation of mesenchymal stem cells (MSCs), and lncRNAs normally bind with microRNA (miRNAs) to function, which might be a breakthrough of regulation of osteogenic differentiation. Our previous studies indicated that expression of several lncRNAs can be increased or decreased significantly in the osteogenic differentiation process of human adipose derived-stem cells (hASCs). However, the interaction among lncRNAs and miRNAs in regulation of osteogenic differentiation of hASCs remains unknown. Based on our previous studies, this project will use microarray technology, series experiments in vitro and in vivo, and methods of mechanism study to confirm the key lncRNAs that regulate the osteogenic differentiation of hASCs, identify the miRNAs that interact with lncRNAs, investigate the effects and mechanisms of the interacted lncRNAs-miRNAs regulation of hASC osteogenic differentiation, and explore the potential molecular targets associated with several key osteogenic signaling pathways. This project is expected to provide a novel way for maxillofacial bone defects repair.