内质网应激在半骺板阻滞术调节骺板软骨内生骨化中的作用及机制研究

项目名称： 内质网应激在半骺板阻滞术调节骺板软骨内生骨化中的作用及机制研究

项目编号： No.81501930

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 吴振凯

作者单位： 上海交通大学

项目金额： 18万元

中文摘要： 半骺板阻滞技术是矫正儿童肢体成角畸形的首选。我们前期的工作发现该技术通过不对称的压应力作用于骺板，调节骺板软骨内生骨化的速度,应力释放后出现“追赶生长”的现象；应力加载和释放的过程伴随骺板软骨细胞的凋亡指数、CHOP和P65等蛋白表达的改变。我们推测，压力调节骺板软骨内生骨化与内质网应激和NF-κB 信号通路有关。本课题拟沿用已成功制备的小型猪半骺板阻滞动物模型，使用免疫组化染色、Real time PCR,、Western blot技术，观察不同时间点和部位骺板内生骨化的速度，静息层、增殖层、肥大层形态构成，基质及ERs相关蛋白、mRNA的表达的变化情况，研究其与应力变化的关系，探讨压应力阻滞骺板内生骨化和应力解除后“追赶生长”的机制；通过阻断ERs、NF-κB通路观察其在应力介导的软骨内生骨化中的作用。本课题对进一步阐明半骺板阻滞术、术后畸形复发的机制，为矫正畸形提供新思路有重要意义。

中文关键词： 半骺板阻滞术；；内质网应激；骺板；软骨内生骨化

英文摘要： Hemiepiphysiodesis, which provides gradual deformity correction, is widely accepted for the management of limb angular deformity in skeletally immature patients with various implant technique. We have found it was hemiepiphysiodesis- induced asymmetric compressive load that acted on the epiphyseal plate and regulated the rate of endochondral ossification. After load removal, catch-up growth was occurred in the eiphyseal plate. Previous studies showed that endoplasmic reticulum stress had a potentially pivotal role to play in the regulation of endochondral ossification. We also have found that the loading and subsequent release induced the change of chondral apoptosis index, as well as the expression of CHOP and P65. We speculate that endoplasmic reticulum stress and NF-κB singnal pathway was activated by compressive load in the process of hemiepiphysiodesis. We plan to observe and measure the epiphyseal matrix synthesis, the rate of growth by endochondral ossification, the composite of resting zone, proliferative zone and hypertrophic zone, the maxtrix-related and endoplasmic reticulum stress-related protein expression, in a miniature pig hemiepiphysiodeseal model. We plan to find the relationship between the change of outcome and compressive load intensity; explore the mechanisms of compressive load- induced retardation of endochondral ossification and catch- up growth after load removal; and test the role of ERs and NF-κB singnal pathway in the process endochondral ossification by inhibited them. The study will comprehensively demonstrate the mechanisms of angular deformity correction and deformity recurrence with hemiepiphysiodesis , providie novel targets for the therapy of angular deformity correction.

英文关键词： hemiepiphysiodesis;endoplasmic reticulum stress ;epiphyseal plate;endochondral ossification