miR-455-3p和C/EBPβ在间充质干细胞成软骨分化中阻抑退变的协同调控机制研究

组织工程软骨在形成与生存中的较早退变仍困扰着临床应用，而较早退变的关键是细胞的调控。我们研究发现软骨细胞退变中转录后和转录（C/EBPβ等）协同调控起着重要作用，而最近我们对人MSCs进行 miRNA芯片筛选发现成软骨分化中miR-455-3p表达升高超过两倍，且生物信息学显示其与C/EBPβ有着对应靶点。本课题以miR-455-3p和C/EBPβ为切入点，研究转录后和转录调控子在人MSCs分化为成软骨细胞过程中阻抑退变、促进分化的协同调控机制：观察不同环境、不同阶段hMSCs成软骨分化时miR-455-3p、C/EBPβ和软骨特征性指标的表达动力学规律，及其与成软骨分化效果和退变效应相关性；研究miR-455-3p与C/EBPβ在hMSCs成软骨分化不同时期的协同调控机制；阐明两者的协同调控机制阻抑hMSCs向成软骨细胞分化中较早退变、促进分化的规律，为解决组织工程软骨退变提供理论基础。

The early degeneration of tissue engineering cartilage during forming and surviving is still a big problem for clinical application, and the key point of this early degeneration in tissue engineering cartilage is cell regulation. We have found that transcriptional (C/EBPβ etc) and post-transcriptional regulation were both involved in the chondrocyte degeneration, and we also found out that miR-455-3p was up-regulated over 2-fold during human MSCs chondrogenesis by miRNA microaray, which was also targeted C/EBPβ from bioinformatics. In this study, we investigate the mechanism of human MSCs chondrogenesis by ordered combinatorial regulation of miR-455-3p and C/EBPβ to improve chondrogenesis and retard chondrocyte degeneration at transcriptional and post-transcriptional level. Firstly, we will observe the expression kinetics of miR-455-3p, C/EBPβ and specific biomarker of cartilage to figure out their regulative rules and relationships with chondrogenesis and degeneration of tissue engineering cartilage. Next, we will clarify circulating co-regulation rules of these factors during hMSCs chondrogenesis at different stages and micro-environment. Lastly, we will prove the rule of retardment of degeneration and improvement of chondrogenesis by regulating this co-regulation mechanism of miR-455-3p and C/EBPβ,to provide the foundation for the control of degeneration of tissue engineering cartilage.