软骨相关ncRNAs组成的ceRNA调控网络共修饰HDAC8在维持软骨特性中的作用机制研究

LncRNA作为竞争性内源RNA与miRNA组成ceRNA网络在间质干细胞成软骨分化和软骨退变过程中发挥重要作用。课题组前期发现miR-455-3p在分化早期促成软骨，但是晚期这一作用明显减弱，可能与lncRNA的协同作用相关。我们进一步经过芯片、实验和信息学筛选出来4个软骨相关lncRNAs可能是ceRNA竞争结合miR-455-3p而拮抗其对HDAC8的调控，从而导致软骨退变的早期发生，而我们初步预实验证实这一可能。本研究拟通过体内外实验从细胞-组织-整体层次阐明软骨相关lncRNAs(AL832767、lincRNA-CCDC93、RP11-160A10.2和RP11-195E11.3)、miR-455-3p和HDAC8组成的ceRNA调控环机制，进而研究干预ceRNA网络使MSCs成软骨分化的早期促进分化，而在中晚期时相抑制退变，突破目前组织工程软骨面临的成软骨稳定性和退变问题。

A competing endogenous RNA (ceRNA) network could be had an important function in chondrogenesis of mesenchymal stem cells and degradation of cartilage, in which the long noncoding RNA (lncRNA) can crosstalk with each other by competing for shared miRNA. We previous identified that miR-455-3p could induce chondrogenesis in early stage, but it was significantly decreased in late stage, and this might be due to its related lncRNAs. We further found that four cartilage-related lncRNAs could regulate the function of miR-455-3p on HDAC8, and thereby impose early degeneration during MSCs chondrogenesis, and our preliminary results support this hypothesis. In this project, we plan to identify this specify cartilage-related ceRNA regulatory network including lncRNAs(AL832767, lincRNA-CCDC93, RP11-160A10.2 and RP11-195E11.3), miR-455-3p and HDAC8 by in vitro and in vivo experiments in cell-tissue-body levels, then regulate this ceRNA network in chondrogenic differentiation to promoting the chondrogenesis and retarding degeneration for maintaining cartilage characteristics.