Lee Hyun Woo, Suh Jung Hee, Kim A Young, Lee Yun Sok, Park So Yun, Kim Jae Bum
Department of Biological Sciences, Research Center for Functional Cellulomics, Seoul National University, Seoul, Korea.
Mol Endocrinol. 2006 Oct;20(10):2432-43. doi: 10.1210/me.2006-0061. Epub 2006 May 25.
Osteogenesis is a complex process associated with dramatic changes in gene expression. To elucidate whether modifications in chromatin structure are involved in osteoblast differentiation, we examined the expression levels of histone deacetylases (HDACs) and the degree of histone acetylation at the promoter regions of osteogenic genes. During osteogenesis, total HDAC enzymatic activity was decreased with significant reduction in HDAC1 expression. Consistently, recruitment of HDAC1 to the promoters of osteoblast marker genes, including osterix and osteocalcin, was down-regulated, whereas histone H3 and H4 were hyperacetylated at those promoters during osteoblast differentiation. Moreover, suppression of HDAC activity with a HDAC inhibitor, sodium butyrate, accelerated osteogenesis by inducing osteoblast marker genes including osteopontin and alkaline phosphatase. Consistently, knockdown of HDAC1 by the short interference RNA system stimulated osteoblast differentiation. Taken together, these data propose that down-regulation of HDAC1 is an important process for osteogenesis.
骨生成是一个与基因表达显著变化相关的复杂过程。为了阐明染色质结构的修饰是否参与成骨细胞分化，我们检测了组蛋白去乙酰化酶（HDACs）的表达水平以及成骨基因启动子区域的组蛋白乙酰化程度。在骨生成过程中，总HDAC酶活性降低，HDAC1表达显著减少。一致的是，HDAC1募集到成骨细胞标记基因（包括osterix和骨钙素）的启动子上的过程被下调，而成骨细胞分化过程中这些启动子上的组蛋白H3和H4发生了超乙酰化。此外，用HDAC抑制剂丁酸钠抑制HDAC活性，通过诱导包括骨桥蛋白和碱性磷酸酶在内的成骨细胞标记基因来加速骨生成。同样，通过短干扰RNA系统敲低HDAC1刺激了成骨细胞分化。综上所述，这些数据表明HDAC1的下调是骨生成的一个重要过程。
