破骨细胞在下颌骨放射性骨坏死形成及预防中的作用

项目名称： 破骨细胞在下颌骨放射性骨坏死形成及预防中的作用

项目编号： No.81470725

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 郑宗梅

作者单位： 首都医科大学

项目金额： 72万元

中文摘要： 下颌骨放射性骨坏死(osteoradionecrosis, ORN)常导致颌面部组织不愈、器官缺损，严重影响肿瘤患者的生存质量,其病变的不可逆、临床表现的多样和治疗的棘手，显示了研究其不明的发病机制并预防其发生的重要性。本研究在前期研究建立了小型猪下颌骨放射性骨坏死模型、初步探讨其发病机制、自体骨髓间充质干细胞移植成功治疗并初步显示有预防作用的基础上，模拟临床肿瘤放疗的方法对小型猪进行照射，放射早期利用二磷酸盐抑制破骨细胞功能,晚期创伤刺激后输注破骨细胞分化因子和单核巨噬细胞集落刺激因子诱导的自体破骨细胞激活骨改建,通过不同时点骨组织病理学,成骨、破骨和血管相关基因和蛋白表达差异，以及观察动物模型下颌骨坏死的发生情况及程度,分析破骨细胞在下颌骨ORN形成及预防中可能发挥的作用, 进一步探讨ORN的发病机制,从而为临床上棘手的下颌骨ORN寻找可能的简单、有效的预防方法。

中文关键词： 破骨细胞；放射性骨坏死；骨改建；下颌骨；预防

英文摘要： Mandibular osteoradionecrosis (osteoradionecrosis, ORN) often result in the maxillofacial tissue and organ defects, serious impact on cancer patients quality of life, the pathological changes of irreversible, the diversity of clinical manifestations and treatment of intractable, shows the importance of the study of the pathogenesis and prevention. On the basis of the previous study that established a large animal model of mandibular ORN in miniature pigs, preliminary discussed the pathogenesis and autologous bone marrow mesenchymal stem cell transplantation showed successful treatment and prevention, We'll use the simulation method of clinical tumor radiation therapy to illuminate of miniature pigs. In the early stage the bisphosphonates will be used to inhibit osteoclast and late after traumatic stimulus infusion the autologous transplanted osteoclasts induced by osteoclast differentiation factor and mononuclear macrophage colony stimulating factor will activate bone reconstruction. Through different point bone tissue pathology, osteogenesis, broken bones and blood vessel related gene and protein expression differences, as well as animal model of osteonecrosis of the jaw, and observation, analysis in mandibular ORN osteoclast formation and may play a role in the prevention, so as to further explore the pathogenesis of ORN, thus for clinical difficult mandibular ORN may be a simple and effective method of prevention.

英文关键词： osteoclast;osteoradionecrosis;bone remodelling;jaw;prevention