LncRNA-XIST, miRNAs和TGF-beta信号通路构成ceRNA机制介导间充质干细胞成软骨分化的表型稳态和表型转换

Tissue engineering is a promising method to repair the degenerated cartilage. The phenotype homeostasis and transition of cartilage remains the key of the area. The appropriate TGF-beta stimulation maintains homeostasis of chondrocyte phenotype, and the excessive TGF-beta stimulation initiates the phenotype transition. However, the underlying mechanisms are not understood. Recent studies revealed that miRNAs, mRNAs and lncRNAs could form ceRNA. The proposer’s previous work proved that miR-193b,381 and lncRNA-XIST participated in the regulation of TGF-beta signaling pathway and chondrogenesis. Based on these works, for the first time a hypothesis is proposed that the ceRNA of lncRNA-XIST, miR-193b,381 and several important genes of TGF-beta signaling pathway mediates the phenotype homeostasis and transition of cartilage under different strength of TGF-beta activation. The current proposal will adopt the RNA immunoprecipitation and the luciferase reporter assay to study the above ceRNA mechanism and its effect. The key problem of the phenotype homeostasis and transition of cartilage would be resolved, and the tissue engineered cartilage would be refined.

组织工程技术是修复软骨退变的理想方法，软骨细胞表型稳态和表型转换是该领域的关键。适当的TGF-beta刺激可维持软骨细胞表型稳态，过度的TGF-beta刺激将导致表型转换。然而其内在机制尚不清楚。最近研究表明，miRNAs, mRNAs和lncRNAs之间可形成ceRNA机制。申请人前期研究发现miRNA-193b,381和lncRNA-XIST参与调控TGF-beta信号通路和成软骨分化，在此基础上首次提出lncRNA-XIST可能与miRNA-193b,381以及TGF-beta信号通路的多个重要基因构成ceRNA机制，介导不同强度TGF-beta信号通路调控软骨细胞表型稳态和表型转换的作用。本项目拟采用RNA immunoprecipitation和荧光素酶报告实验等技术从体内和体外层面研究上述ceRNA机制及作用，有望解决软骨细胞表型稳态和表型转换的问题，改善组织工程软骨性能。