颌面部骨缺损严重影响患者的生存质量，组织工程有望为骨缺损修复提供新的模式。但如何高效、特异地诱导种子细胞成骨分化是一核心问题。与BMP2等常用因子相比，NELL1不仅具有高效成骨诱导作用，且作用于RUNX2下游，无异位成骨效应，具有更突出的应用价值，但其机制尚不明了。最新文献报道lncRNAs参与调控干细胞成骨分化，并常与miRNAs以ceRNAs形式相互作用进行调控。课题组前期研究证实，在NELL1促人脂肪干细胞成骨分化中多个相关lncRNAs表达明显上调或下调，但尚未见该过程中lncRNAs的调控作用及机制研究。本课题拟通过高通量筛选、体外及体内系列实验验证、作用机制探索的技术路线确定在NELL1促人脂肪干细胞成骨分化中调控作用最优的lncRNAs，研究并鉴定与之交互作用的miRNAs，明确lncRNAs-miRNAs作用机制及其与成骨相关通路之间的交叉对话，为骨再生修复提供新的思路。

Maxillofacial bone defects severely affect the patients' quality of life. Tissue engineering is expected to provide a new model of bone defect repair. However, how to efficiently and specifically induce osteogenic differentiation of seed cells is a key issue. Compared with bone morphogenetic protein 2 (BMP2) and some other common osteogenic growth factors, neural EGFL like 1 (NELL1) has a highly efficient osteoinductive effect, functions as a key mediator downstream of RUNX2, and cannot induce ectopic bone formation. Therefore, NELL1 has a more prominent value for bone regeneration. But the mechanism of NELL1 on osteogenic induction is still unclear. Recent reports demonstrated that some long noncoding RNAs (lncRNAs) were involved in the regulation of osteogenic differentiation of stem cells by interaction with microRNAs (miRNAs) and acting as competing endogenous RNAs (ceRNAs). Our preliminary experiments indicated that the expressions of several lncRNAs could be increased or decreased significantly during osteogenic differentiation of human adipose derived-stem cells (hASCs) induced by NELL1. However, up to now, to our knowledge, no study has been reported about the roles of lncRNAs in NELL1-induced osteogenic differentiation. Based on our previous transcriptome sequencing study, this project will use series experiments both in vitro and in vivo, and methods of mechanism study to confirm the key lncRNAs that regulate the NELL1-induced hASC osteogenic differentiation, 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 crosstalk of lncRNAs-miRNAs with key osteogenic signaling pathways. This project is expected to provide a novel potential way for bone regeneration.