镁调控H型血管促进成骨的机制研究

How to effectively promote osteogenesis is one of the most important unsolved problems in the field of orthopedics. Our group developed a new type of magnesium alloy and confirmed that it can efficiently promote osteogenesis. It was confirmed through previous studies that its osteogenesis was related to local type H vessels. Type H vessels are a newly discovered subtype of blood vessels which are closely related to bone formation. Our group screened and verified differentially expressed miRNAs in Type H vascular endothelial cells after magnesium intervention. It was found that miR-455-3p and miR-182-5p are related to magnesium-mediated osteogenic bone formation by targeting the Notch pathway. We speculate that magnesium-mediated miRNAs modulate the Type H vessel Notch pathway to promote osteogenesis. This research intends to explore the mechanism of magnesium-mediated miRNA regulation of Type H vessels to promote osteogenesis from three levels of animals, cells and molecular biology: 1. To clarify the relationship between magnesium osteogenesis and Type H vascular Notch pathway; 2. To clarify the screened miRNAs (miR-455-3p and miR-182-5p) target the mechanism of binding and regulation of the Notch pathway. 3. The specific Aptamer agomiR/antagomiR was constructed to specify that the exogenous miRNAs target the Notch pathway to promote the osteogenic effect. This project intends to thoroughly investigate the mechanism of magnesium formation and lay a solid foundation for the basic research of bone formation and the clinical application of magnesium.

如何有效促进成骨是骨科领域亟需解决的医学难题。本课题组研发新型镁合金并证实能促进成骨，前期研究证实其成骨与局部H型血管相关。H型血管是一种新发现的血管亚型，与骨形成密切相关。本课题组对镁干预后H型血管内皮细胞内差异表达的miRNA进行筛选并验证，发现miR-455-3p及miR-182-5p通过靶向Notch通路与镁介导下成骨相关。因此，我们推测镁通过介导miRNA调节H型血管Notch通路促进成骨。本课题拟从动物、细胞及分子生物学三个层面探讨镁促进成骨的具体机制：1、明确镁成骨与H型血管内Notch通路相关性；2、阐明所筛选的miRNA靶向结合并调控Notch通路的机制；3、构建特异性Aptamer agomiR/antagomiR，明确外源性miRNA靶向Notch通路促进成骨效应。本项目拟深入探讨镁成骨机理，为促成骨基础研究和镁的临床应用打下坚实的基础。

如何有效治疗骨折不愈合及骨缺损已成为骨科学领域中亟需解决的医学难题。H型血管是一种近年来新发现的骨特异性血管亚型，被报道与骨形成密切相关。本课题研发了新型镁合金材料并证实其成骨与局部H型血管相的生成有关。此外，本课题深入探究了镁促成骨及成血管的机理，研发了多种新型镁基合金并对其理化性质、成骨性能、抗菌/抗骨肿瘤特性进行了探讨，为促成骨的基础研究和镁基材料的临床应用打下坚实的基础。此外，我们的研究表明已获FDA批准并广泛使用的“老药”二甲双胍可能在骨再生的临床应用上有新的用处。