椎间盘退变（IVDD）是临床上最常见的脊柱慢性疾病，软骨终板退变是IVDD的主要病理基础之一，但相关的分子机制尚不清楚。我们前期研究发现IVDD终板中软骨细胞的关键转录因子SOX9表达降低，SOX9启动子H3K27位点甲基化增高，进一步筛选发现该位点甲基化受组蛋白甲基化转移酶EZH2表达调控。据此，我们假设：退变因素通过上调EZH2沉默SOX9基因从而引起终板软骨细胞退变。本课题拟在前期结果的基础上从确认现象、探索机制和逆转干预三个方面展开研究：（1）明确EZH2在IVDD中的表达变化，并通过基因转染和基因沉默手段在细胞实验中研究EZH2对终板软骨细胞功能的调控；（2）通过ChIP、qPCR等技术研究EZH2调控SOX9表达的分子机制；（3）应用shEZH2慢病毒及EZH2抑制剂在动物模型中验证其对IVDD的治疗效果。本研究可为临床以EZH2为靶点治疗或预防IVDD提供新思维、新手段。

Intervertebral disc degeneration (IVDD) is the most common spine chronic disease. Endplate cartilage degeneration is one of the main pathological basis of the IVDD, however, the molecular mechanisms remain unclear. The transcription factor SOX9 has an essential role during the sequential steps of chondrocyte differentiation. Our previous study found that the expression of EZH2 significantly reduced in IVDD Endplate cartilage, meanwhile, there was a significant increase in H3K27 trimethylation at SOX9 promoters, moreover, the H3K27 trimethylation was regulated by the histone methyltransferase EZH2. Accordingly, we hypothesize that increased expression of EZH2 leads to endplate cartilage degeneration via repressing SOX9 gene. To verify this hypothesis, we will : (1)study the expression of EZH2 in IVDD，and the effects of EZH2 on chondrocytes degeneration using the technology of gene transfection and gene silencing ;(2) explore the molecular mechanisms of EZH2 regulates SOX9 expression by ChIP、qPCR,et al; (3)verify the therapeutic effect of EZH2 inhibitor in IVDD animal models. We explore the role of EZH2 in the pathogenesis of IVDD and may supply a new target for IVDD therapy.