颌骨放射性骨坏死(ORN)是头颈肿瘤放疗后常见的一种并发症，放疗区的组织内常出现"低氧、低血运、低细胞"现象，这使 ORN 性颌骨缺损的修复重建面临严峻挑战。文献报道 miRNAs 在血管发生及形成中起重要作用。研究者发现 miR-21与血管生长密切相关，其通过HIF-1α/VEGF通路完成血管再生。但是，miR-21与骨形成的关系，迄今国内外尚未报道。我们推测 miR-21是多重作用因子，具有促进血管形成和骨生成的双重调控作用。这种假说在预实验中得到初步验证，我们首次发现miR-21具有促进间充质干细胞血管及骨向分化作用。鉴于此，本项目拟构建大鼠及山羊ORN动物模型，应用慢病毒载体转染、基因芯片检测、血管化组织工程骨构建及牙种植体植入等技术，从mRNA-蛋白-小动物-大动物4层次验证我们的假说，阐明miR-21介导的血管化组织工程骨对ORN生物功能重建作用及其信号转导通路的调控。

Jaw osteoradionecrosis (ORN) is a common complication of radio-therapy during head and neck tumors treatment. Meanwhile, low oxygen levels, low blood supply, and low cell counts are often observed in ORN area, resulted with significant challenges to the functional reconstruction of patients who suffer from severe deformities or jaw defects caused by ORN. Previous studies showed that miRNAs play an important role during the procedure of angiogenesis and vascularization. The researchers found that miR-21 is closely related with growth of blood vessel and this process mainly depends on HIF-1α/VEGF pathway to complete revascularization. However, till now, the relationship of miR-21 and bone formation has not been reported clearly. We hypothesize that miR-21 is a multiple effect factor, and can not only promote the formation of blood vessels, but also enhance bone formation. This hypothesis has been partly verified in the preliminary experiments. We found miR-21 can promote bone marrow mesenchymal stem cells double differentiation of angiogenesis osteogenesis for the first time. In view of above data, this work intends to establish the ORN animal models in rats and goats, and to confirm our hypothesis on 4 different levels (i.e., mRNA, proteins, small animals, and large animals) via lentiviral vector transduction, gene chips detection, vascularized tissue bone construction, and dental implant. This study will elucidate the effect of using miR-21-mediated tissue engineered bone to reconstruct oral biological function of ORN bone defects and regulatory function of signal transduction pathway.