miR-539在OPN调控未发育成熟颅骨缺损修复中的作用及机制

Skull defects are common clinical problems, in particular there is considerable controversy about time in reparation of skull defects of children, and it was needed to find new ideas and means to facilitate the healing of skull defects in children. Osteopontin (OPN) plays an important role in the development of the skull through participating in the skull defect regenerative process. Studies have found that miRNA is closely related to bone metabolism, can be involved in regulating multiple genes and signaling pathways in metabolism of osteoblast, but has not been seen the report about miRNA acting on the OPN to regulate osteoblast differentiation and maturation. Our early work focused on the research of morphology and patched teratogenesis of immature skull defects, and we recently found miR-539 most likely to be involved in the regulation of OPN by use of miRNA target gene prediction software. The mouse primary osteoblast cells model and goat immature skull defects model were used in this project, together with tissue pathology, molecular biology and bioinformatics methods, from the levels of tissue, cells, molecules and signal transduction pathway, and We not only verified the hypothesis that OPN is miR-539 target-gene,but also explored the role and mechanism of miR-539 regulating OPN in immature skull defect repair process, and provided molecular basis for clinical diagnosis and treatment of skull defect in children.

颅骨缺损是临床常见问题，尤其小儿颅骨缺损的修复存在极大争议，急需探寻新的思路和手段来促进小儿颅骨缺损的愈合。骨桥蛋白（OPN）在颅骨发育中起重要作用，可参与颅骨缺损再生过程。研究已发现miRNA与骨代谢密切相关，可调控多种基因及信号通路蛋白来参与成骨细胞代谢，但国内外尚未见miRNA作用于OPN来调控成骨细胞分化的报道。我们的前期工作主要集中于未发育成熟颅骨缺损后形态学和修补后致畸作用的研究，近期利用miRNA的靶基因预测软件发现miR-539最有可能参与OPN的调控。本项目通过采用小鼠原代颅骨成骨细胞和山羊未发育成熟颅骨缺损模型，利用组织病理学、分子生物学技术和生物信息学方法，从组织、细胞、分子和信号传导途径等层面，验证OPN是miR-539的靶基因的假说，并深入研究miR-539在OPN调控未发育成熟颅骨缺损修复过程中的作用及机制，为临床小儿颅骨缺损的治疗新策略提供分子基础和理论依据。

颅骨缺损是临床常见问题，尤其小儿颅骨缺损的修复存在极大争议，急需探寻新的思路和手段来促进小儿颅骨缺损的愈合。研究已发现miRNA与骨代谢密切相关，可调控多种基因及信号通路蛋白来参与成骨细胞代谢，我们研究发现miR-539的表达与骨的形成和钙化关系密切，利用颅骨缺损山羊模型发现，miR-539的靶基因OPN和DLX-2在新成骨中表达增长，同时培养的成骨细胞MC3T3-E1发现与颅骨缺损山羊模型相同的结果。本研究并深入研究miR-539在调控未发育成熟颅骨缺损修复过程中的作用及机制，为临床小儿颅骨缺损的治疗新策略提供分子基础和理论依据。