Ihh-PTHrP信号轴在髁突软骨中的时空表达特征及其调控机制

项目名称： Ihh-PTHrP信号轴在髁突软骨中的时空表达特征及其调控机制

项目编号： No.81200766

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 蔡协艺

作者单位： 上海交通大学

项目金额： 23万元

中文摘要： 髁突的生长改建是多种治疗方式的生物学基础，其改建能力在不同的年龄段有明显的差异，这种差异关乎治疗模式和治疗时机的选择,并影响治疗效果。力载荷在软骨改建中起重要作用，业已证实压应力是导致髁突改建的关键而敏感的力量之一，但软骨细胞识别应力信号并发生生物应答反应的具体机制目前尚不清楚。Ihh-PTHrP信号轴是近年来骨骺生长板软骨内成骨调控机制研究的热点之一，但其在髁突软骨中的研究甚少。本研究旨在从蛋白和基因水平观察Ihh-PTHrP信号轴在不同发育期髁突软骨的表达和定位，信号抑制和增强对下游分子表达和髁突软骨细胞生物学行为的影响，压应力负荷对Ihh-PTHrP信号轴表达及髁突软骨细胞增殖、分化和凋亡的影响，以期阐明其在出生后髁突软骨中的时空表达特征、调控机制以及不同髁突软骨细胞所能承受的压应力负荷，从而为研究髁突在不同发育期的生长改建能力、影响因素及治疗时机的选择提供基础理论支持。

中文关键词： 髁突；软骨细胞；印第安刺猬蛋白；甲状旁腺激素相关蛋白；压应力

英文摘要： Condylar remodeling is the biological basis of a variety of treatment modalities for oral disease. The capacity of remodeling is significantly different at different ages, which might affect the choice of treatment modalities, timing of treatment, and its therapeutic effects. Stress load plays an important role in cartilage remodeling. Many studies have confirmed that the compressive stress is one of critical and sensitive forces that lead to condylar remodings. However, the detailed mechanism is still unclear as to how the chondrocytes recognize the stress signals and start the biological responses. Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP) participate in a negative feedback loop that regulates chondrocyte proliferation, differentiation and apoptosis both in embryonic and postnatal growth cartilage. However, it has seldom been studied in condylar cartilage. The aim of this study is to explore expression and location of markers of Ihh-PTHrP feedback loop in different developmental stages of condylar cartilage using the techniques of immunohistochemistry, in situ hybridization, RT-PCR and Western blot technique, to evaluate the influence on proliferation, differentiation and apoptosis of chondrocyte by inhibiting the pathway, to detect the changes of markers of Ihh-PTHrP feedback loop

英文关键词： condyle；chondrocyte；Ihh；PTHrP；compressive stress