镇祥燕,余诗宇,陈康武

目的：探讨异常力学刺激诱导软骨细胞退变过程中组蛋白H3K9me3及其甲基转移酶Suv39h1的作用机制。方法：分离培养小鼠原代软骨细胞，采用体外循环牵张加载系统建立异常力学刺激模型，以5%幅度为对照、12%幅度为过度力学刺激。通过免疫荧光染色和实时定量PCR检测Ⅱ型胶原和X型胶原表达变化；采用Western blot和实时定量PCR检测H3K9me3及相关调控酶的表达。进一步通过siRNA干扰Suv39h1，观察其对H3K9me3水平及软骨细胞退变的影响。结果：过度力学刺激显著降低Ⅱ型胶原表达并上调X型胶原表达，提示软骨细胞发生退变，同时H3K9me3水平明显升高。多种H3K9me3相关酶中，Suv39h1表达显著上调。干扰Suv39h1后，H3K9me3水平降低，Ⅱ型胶原表达部分恢复，X型胶原表达减少，软骨细胞退变得到缓解。结论：异常力学刺激可通过Suv39h1介导的H3K9me3上调促进软骨细胞退变，Suv39h1/H3K9me3轴可能成为力学异常相关软骨退变的潜在干预靶点。

力学刺激；软骨细胞退变；表观遗传；H3K9me3；Suv39h1

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