椎间盘退行性病变发病机制及治疗的研究与终板内软骨细胞的组成和特性密切相关。本课题组前期研究发现人退变椎间盘软骨终板内存在干细胞（DCESCs），并且其成骨/软骨分化性能显著高于同来源的间充质干细胞。可变剪接是转录后修饰的一个重要过程,在干细胞生理调控方面有关键的作用。本研究拟以DCESCs作为研究对象，对其进行成骨/软骨的诱导分化，并对分化后的成骨/软骨细胞进行鉴定，用外显子芯片技术分析DCESCs向骨/软骨诱导分化前后发生变化的可变剪接事件，对获取的可变剪接变异体进行GO分析和验证。可变剪接对DCESCs分化调控机制研究以胰岛素受体(IR)可变剪接为模型，拟应用基因、蛋白水平等检测手段分析IR剪接变异体（IR-A/-B）在调控分化方面的功能，以及DCESCs成骨/软骨分化过程中IR不同剪接变异体表达的调控机制。本研究所取得的成果将DCESCs成骨/软骨分化调控研究引入到转录后修饰的水平。

The pathogenesis and treatment of intervertebral disc degenerative diseases are closely related to composition and properties of chondrocytes in intervertebral disc cartilage endplate. Our previous study found that there were stem cells in degenerated intervertebral disc cartilage endplate(DCESCs), and their osteogenic/chondrogenic differentiation potential was stronger than mesenchymal stem cells from the same source. Alternative splicing is an important process of post-transcriptional modification, and plays key roles in physiological regulation of stem cells. This study will focus on the regulation of osteogenic/chondrogenic differentiation of DCESCs, and splicing events will be detected by exon array before and after osteogenic/chondrogenic differentiation. Results of exon array are to be verified and further analyzed by GO analysis. Alternative splicing of insulin receptor (IR) will be used as a model to study the mechanisms of DCESCs differentiation regulated by alternative splicing. Expression and function of IR splicing variants IR-A/B and mechanisms of IR alternative splicing during DCESC osteogenic/chondrogenic differentiation will be illustrated using techniques of molecular biology of gene and proteins. Results of this research will elucidate mechanisms of post-transcriptional modification of chondrogenic and osteogenic differentiation of DCESCs. In addition, this study will provide new theoretical insight for the target-directed treatment and prevention of degenerative disc diseases.