组织工程软骨纤维化导致关节软骨修复不佳，Sox9-Runx2失衡引起的种子细胞肥大化是其主因，但机制不详,故本课题以此切入探求延缓软骨纤维化的机制。在证实miR-145调控Sox9参与软骨分化的基础上，预实验发现肥大进程中miR-145和miR-29b显著下调。基于miR-29b靶分子HDAC4是调控Sox9-Runx2平衡的负反馈分子，因此提出"miR-29b/145调控Sox9-Runx2平衡参与软骨细胞肥大化"假说。拟利用293细胞检测miR-145和miR-29b相互作用及可能方式；利用MSCs进行该miRNA对的细胞学定位；观察功能干预下，其对MSCs成软骨分化中增殖、分化、肥大化等表型的影响，明确对Sox9-Runx2平衡的改变；在体裸鼠种植和软骨修复模型，阐述阻抑或上调该分子对对软骨形成的效应改变。本研究将为干细胞软骨分化调控积累基础资料，也可为工程化软骨修复提供理论指导。

Tissue engineering cartilage fibrosis always lead to unsatisfied result in articular cartilage repairing, this could be mainly attribute to seed cell hypertrophy caused by the unbalanced expression of Sox9-Runx2. But the molecular mechanism remain unknown. The project proposes to figure out the mechanism and designs to delay the process of cartilage fibrosis. As miR-145 has been verified to regulate Sox9 in chondrogenic differentiation, our previously study showed a significant decrease in expression of miR-145 and miR-29b during the hypertrophy process. And HDAC4 is a negative feedback factor in the regulation of Sox9-Runx2 balance while HDAC4 is also a target of miR-29b. So we propose a hypothesis that "miR-29b/145 participate in chondrocytes hypertrophy by regulating Sox9-Runx2 balance". In this project, 293 cell will be cultivated to detect the interaction between miR-145 and miR-29b. Mesenchymal stem cells will be utilized for miR-145 and miR-29b localization. Under gain of function and loss of function method, we'll study how miR-145 and miR-29b would affect the proliferation, differentiation,hypertrophy process of mesenchymal stem cells and clarify their role in Sox9-Runx2 balance. By utilizing nude mice subcutaneously implantation and cartilage defect repair model, the effects during cartilage formation by block or upregulate miR-145 and miR-29b are expected to be indicated. This research will provide knowledge for the regulation of chondrogenic differentiation of stem cell as well as offer theoretical support for cartilage repair in biomedical engineering field.