SOX9介导TGF-β/Smads/wnt和β-catenin信号通路调控青少年椎体骺板软骨的分化

项目名称： SOX9介导TGF-β/Smads/wnt和β-catenin信号通路调控青少年椎体骺板软骨的分化

项目编号： No.81472145

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： 张宏其

作者单位： 中南大学

项目金额： 72万元

中文摘要： 椎体骺板软骨定向分化是青少年脊柱线性生长的关键，其调控机制尚不清楚。据研究，SOX9和β-catenin信号传递在软骨分化过程中发挥重要作用。我们前期研究也证明，TGF-β/Smads/wnt信号通路调控椎体线性生长。据此，我们推断：SOX9调节TGF-β/Smads/wnt和β-catenin信号通路调控青少年椎体骺板软骨细胞定向分化为成骨细胞，进而调控其脊柱的线性生长。我们拟采用RNAi技术，建立SOX9等基因沉默细胞模型和动物模型，并用SOX9表达载体转染基因敲除小鼠，于体外和体内分别研究SOX9对青少年椎体骺板分化的作用，及其对主要信号因子的调控，观察椎体骺板软骨细胞定向分化的情况，以期揭示SOX9介导的TGF-β/Smads/wnt和β-catenin信号通路在青少年椎体线性生长发育中的调控机制，为青少年脊柱发育异常等疾病的诊治寻找新的早期诊断候选标记物和治疗的新靶点奠定基础。

中文关键词： 信号通路；软骨细胞；生长板；青少年；脊柱

英文摘要： Adolescent linear growth depends on the differentiation of spinal vertebral epiphyseal plate , but the regulatory mechanism is unclear. to data, SOX9 and β-catenin signaling plays an important role in the differentiation.of cartilage. Our previous studies had proved that, vertebral linear growth is regulated by TGF-β/Smads/wnt signaling pathways.Accordingly, we assume that SOX9 regulate differentiation of adolescent vertebral epiphyseal plate chondrocytes directed to differentiate into osteoblasts by mediating TGF-β/Smads/wnt and β-catenin signaling pathway, regulating the spinal vertebrae linear growth. Our approach is that SOX9-shRNA gene silencing lentivirus vector were built with the RNAi technology, and transfected into chondrocytes and mice to establish SOX9 gene silencing cell and animal models,while SOX9 lentivirus vector was transfected into knockout mice,to study the role of regulation of SOX9 to youth vertebral epiphyseal plate differentiation, and the regulation of major signaling factors to observe the differentiation of vertebral epiphyseal plate chondrocyte in vitro and in vivo, respectively. Expected, experiments may reveal the function ofSOX9 in regulating the linear growth of the adolescent vertebral spine by mediating TGF-β/Smads/wnt and β-catenin signaling pathway,. lay the foundation for candidate therapeutic targets, clinical decision-making and therapeutic markers.

英文关键词： singaling pathway;chondrocytes;growth plate;adolescent;spine