lncRNA-Bvht靶向吸附miR-133a-3p调控H型血管Rbpj表达和Notch通路促进骨修复的机制研究

How to effectively promote bone repair is one of the most important unsolved problems in the field of orthopedics. Studies have found a novel subtype of blood vessels (called type H blood vessels) and confirmed that local type H vessels are closely related to osteogenesis. Long non-coding RNAs (lncRNAs) as competitive endogenous RNAs play an important regulatory role in gene expression. Based on the data of gene chip and dual-luciferase reporter assay, we proposed that lncRNA-Bvht could promote the expression of Rbpj gene by competitive binding miRNA-133a-3p, thus promoting Notch signaling pathway in type H endothelial cells and finally increasing bone repair. Based on the above preliminary study, this project intends to study: 1. To clarify the relationship among lncRNA-Bvht, miR-133a-3p and Notch pathway in type H endothelial cells. 2. To elucidate the detailed mechanism of miRNA-133a-3p targeting Rbpj mRNA to activate Notch signaling pathway. 3. To construct aptamers and clarify that exogenous lncRNA or miRNA can promote bone repair by regulating Notch pathway. The implementation of this project will provide new theories and directions for the mechanism of type H vessels promoting bone repair.

如何有效促进骨修复是骨科领域亟需解决的医学难题。已有研究发现一种新型的血管亚型称为H型血管，并证实其与成骨密切相关。长链非编码RNA(lncRNA)作为竞争性内源RNA在基因表达中起重要调控作用。本课题基于基因芯片筛选和双荧光素酶报告基因实验提出如下假说“lncRNA-Bvht通过竞争性结合miR-133a-3p调控Rbpj mRNA表达，从而调控H型血管中Notch信号通路，进而促进骨修复”。本项目在前期研究基础上，拟从动物、细胞、分子生物学三个层面进行研究：1、明确lncRNA-Bvht与H型血管miR-133a-3p和Notch通路的相关性；2、阐明miR-133a-3p靶向结合Rbpj mRNA调控Notch信号通路的详细机制；3、构建lncRNA和miRNA核酸适配体，明确其可通过调控Notch通路促进骨修复。本课题的实施将会为H型血管促进骨修复的机制研究提供新的理论和方向。

如何有效促进骨修复是骨科领域亟需解决的医学难题。已有研究发现一种新型的血管亚型称为H型血管，并证实其与成骨密切相关。长链非编码RNA(lncRNA)作为竞争性内源RNA在基因表达中起重要调控作用。本课题基于基因芯片筛选和双荧光素酶报告基因实验提出如下假说“lncRNA-Bvht通过竞争性结合miR-133a-3p调控Rbpj mRNA表达，从而调控H型血管中Notch信号通路，进而促进骨修复”。本项目在前期研究基础上，拟从动物、细胞、分子生物学三个层面进行研究：1、明确lncRNA-Bvht与H型血管miR-133a-3p和Notch通路的相关性；2、阐明miR-133a-3p靶向结合Rbpj mRNA调控Notch信号通路的详细机制；3、构建lncRNA和miRNA核酸适配体，明确其可通过调控Notch通路促进骨修复。本课题的实施将会为H型血管促进骨修复的机制研究提供新的理论和方向。