应力负荷介导下Ihh/PTHrP信号轴对髁突前软骨干细胞分化的影响及作用机制

The remodeling of condyle cartilage was one of the key points which influenced the prognosis of temporomandiublar joint disorder. The precartilaginous stem cells (PSCs) were found in condyle for long-term, remaining the differentiation porential even in adult. PSCs played an important role in the development of condyle and cartilage remodeling. The objective of this research was to detect the effect of masticatory load on the distribution, differentiation and proliferation of PSCs. We attempted to found the mechanism and relationship of the intermittent hydrostatic pressure and Ihh/PTHrP signal pathway on the differentiation of PSCs, by the methods of the laser scanning confocal microscope, micro-CT, immunomagnetic separation, flow cytometry, Western Blot and RT - PCR.The research would be benefit to find out the pathway of the differentiation of PSCs when the patients were suffered with the abnormal stress load such as temporomandibualar joint disorder. How to induce the adaptive remodeling would be critical to clinical treatment of TMD.

髁突软骨的适应性改建是影响颞下颌关节紊乱病患者病程转归的关键因素。髁突软骨内储存的前软骨干细胞长期保持向软骨细胞定向分化的潜能，在髁突形成、生长发育和软骨损伤后修复中具有重要作用。本研究采用激光共聚焦显微镜、显微CT、免疫磁珠分选技术、流式细胞仪、蛋白质和核酸分析等研究技术，分析生长发育期不同咀嚼应力负荷对兔髁突前软骨干细胞的分布、分化和增殖的时空表达的影响，寻找咀嚼应力负荷和Ihh/PTHrP信号轴的内在联系，探讨间歇静压力介导下Ihh/PTHrP信号轴通路对髁突前软骨干细胞向软骨细胞定向分化的作用机制。本研究有助于探寻如何在异常应力负荷下适时启动髁突前软骨干细胞分化增殖，引导髁突软骨实现自发性的适应性改建，从而为颞下颌关节紊乱病提供新的治疗思路和方法。

本研究建立咀嚼负荷降低的发育期幼兔动物实验模型，采用激光共聚焦显微镜、显微CT、免疫组化、蛋白质和核酸分析等研究技术，分析生长发育期不同咀嚼应力负荷对兔髁突前软骨干细胞的分布、分化和增殖的时空表达的影响，寻找咀嚼应力负荷和Notch信号轴、Ihh/PTHrP信号轴内在联系，探讨咀嚼压力介导下Notch信号轴通路、Ihh/PTHrP对髁突前软骨干细胞向软骨细胞定向分化的作用机制。本项目基本按照原计划进行，已发表国内一级期刊1篇，二级期刊论文2篇，参加国际会议并交流3次，培养硕士研究生2人。本研究有助于探寻如何在异常应力负荷下适时启动髁突前软骨干细胞分化增殖，引导髁突软骨实现自发性的适应性改建，从而为颞下颌关节紊乱病提供新的治疗思路和方法。