CircRNA-vgll3介导的脂肪间充质干细胞修复眼眶骨缺损及其作用机制研究

Orbital bone defects can lead to visual dysfunction and facial deformity, and it is difficult to heal itself after the defect. Studies have shown that adipose derived mesenchymal stem cells (ADSC) can promote bone defect repair, and circRNA plays an important role in stem cell osteogenesis. Previous studies found that circRNA-vgll3 (ciR-vgll3) was closely related to osteogenic differentiation of ADSC, and in this process ciR-vgll3 was closely related to small non encoding RNA (miR-326-5p) and its target gene Igta5 (an important regulatory factor of osteogenic differentiation of stem cells). During osteogenic differentiation, the expression of ciR-vgll3 increased gradually, ciR-vgll3 overexpression could significantly increase ADSC osteogenic gene expressions, and silencing ciR-vgll3 inhibited their expression levels. CiR-vgll3 regulates the osteogenic differentiation activity of ADSC through the competitive binding of miR-326-5p to regulate the translation of the target gene Igta5 of miR-326-5p.The aim of this study is to explore the mechanism of ciR-vgll3 promoting osteogenic differentiation of ADSC from different levels, including gene, protein and small animal bone defect and large animal orbital bone defect models, and systematically evaluate its osteogenic potential, which is expected to provide new ideas for clinical orbital bone defect repair.

眼眶骨缺损常导致视功能障碍和面部畸形，缺损后难自愈。研究表明脂肪间充质干细胞（ADSC）成骨分化能促骨缺损修复，而环状RNA（circRNA）在干细胞成骨分化中发挥重要作用。课题组前期研究发现circRNA-vgll3（ciR-vgll3）与ADSC成骨分化关系密切，而在此过程中ciR-vgll3与微小非编码RNA（miR-326-5p）及其靶基因Igta5（干细胞成骨分化重要调控因子）关系紧密：成骨分化中，ciR-vgll3表达逐渐升高，过表达它能显著上调ADSC成骨基因表达，而沉默它则抑制其表达；ciR-vgll3通过竞争性结合miR-326-5p调控后者靶基因Igta5翻译，进而调控ADSC成骨活性。本课题拟从基因、蛋白及小动物骨缺损和大动物眼眶骨缺损模型不同层次，探讨ciR-vgll3促ADSC成骨分化的作用机制，并系统评估其促成骨能力，可望为解决临床眼眶骨缺损修复难题提供新思路。

眼眶骨缺损常导致视功能障碍和面部畸形，缺损后难自愈。研究表明脂肪间充质干细胞（ADSC）成骨分化能促骨缺损修复，而环状RNA（circRNA）在干细胞成骨分化中发挥重要作用。课题组研究发现circRNA-vgll3（ciR-vgll3）与ADSC成骨分化关系密切，而在此过程中ciR-vgll3与微小非编码RNA（miR-326-5p）及其靶基因Itga5（干细胞成骨分化重要调控因子）关系紧密：成骨分化中，ciR-vgll3表达逐渐升高，过表达它能显著上调ADSC成骨基因表达，而沉默它则抑制其表达；ciR-vgll3通过竞争性结合miR-326-5p调控后者靶基因Itga5翻译，进而调控ADSC成骨活性。本课题从基因、蛋白及小动物骨缺损和大动物眼眶骨缺损模型不同层次，探讨了ciR-vgll3促ADSC成骨分化的作用机制，并系统评估其促成骨能力，可望为解决临床眼眶骨缺损修复难题提供新思路。.论文发表方面：在此项目的资助下,课题组已在《Advanced Materials》、《Small Methods》、《Cell Death & Differentiation》等SCI收录杂志发表论文11篇（均标注有本项目的资助编号，且本项目的负责人均为发表论文的通讯作者或共同通讯作者）。..学术交流方面：我们多次参加全国眼科年会和全国眼科基础研究大会以及眼科相关的各种学术会议。..研究生培养方面：从事本项目研究的研究生共7名，已毕业5名。