中文摘要：

利用骨髓来源的干细胞（bone marrow derivedstemcells，BMSCs）作为骨组织工程种子细胞来修复骨缺损已成为研究热点．转录因子是影响骨生长的重要因素，其中Runx2（Runt．relatedtranscriptionfactor2）是参与成骨细胞分化与骨形成的重要转录因子之一．近年来，表观遗传学在发育生物学及干细胞分化过程中的调控机制倍受重视．而Runx2是否受到表观遗传学调控尚未见报道．本研究采用real-timeRT-PCR检测Runx2的mRNA表达，ChIP（chromatinimmunoprecipitation）结合real—timeRT—PCR检测Runx2基因启动子区甲基化水平及组蛋白修饰水平的变化．结果显示，BMSCs在成骨诱导分化中Runx2的mRNA表达在3d达到高峰，之后下降；同时在BMSCs成骨分化第3d，与转录激活相关的组蛋白修饰乙酰化H3K9和三甲基化H3K4均升高；而与转录抑制相关的组蛋白修饰三甲基化H3K9降低．另外检测还显示，Runx2启动子区域乙酰化H3K9和三甲基化H3K4募集增加，而三甲基化H3K9募集降低．Runx2启动子区域DNA甲基化修饰程度降低．上述结果表明，BMSCs在成骨分化过程中Runx2的表达上调，其基因启动子区域呈现促进基因表达的表观遗传修饰变化．由此推断，表观遗传调控在BMSCs成骨分化过程中具有一定作用，它将为提高BMSCs的成骨分化效率提供线索．

英文摘要：

Bone marrow stem cells （BMSCs） have been considered an ideal cell source for bone tissue engineering for their natural osteoprogenitor characteristics. However, current limitations hinder BMSCs- based clinical applications. Osteogenic differentiation of MSCs is a complex process regulated by a number of transcription factors. Epigenetic regulation has recently been considered as an important mechanism to influence stem cell differentiation. Runt-related transcription factor 2 （Runx2） is essential for osteoblast differentiation and bone formation. Whether the Runx2 expression is regulated by epigenetic modifications has not been elucidated. We found that the maximum expression of Runx2 was at day 3 of osteogenic induction, with increased transcription-permissive histone modifications of H3K9 acetylation and H3K4 trimethylation and decrease in transcription-repressive histone modification of H3K9 trimethylation. The recruitments of acetylated H3K9 and trimethylated H3K4 on the Runx2 promoter were increased following 3 days osteogenic induction, whereas the recruitment of trimethylated H3K9 and DNA methlation were decreased. The histone modifications and DNA methylation was able to theoretically promote the mRNA expression of Runx2 during BMSCs osteogenesis. This study may add new insights into the promotion of BMSCs osteogenesis.