The analysis of epigenetic regulation of osteoblastogenesis induced by BMP-2

骨形态发生蛋白-2 （BMP-2）刺激成骨细胞分化，但抑制C2C12成肌细胞的肌发生分化。为了评估BMP-2诱导成骨细胞分化的重要基因，我们对添加或不添加BMP-2处理4天的C2C12细胞进行了微阵列分析。我们发现，与未处理的细胞相比，BMP-2处理的C2C12细胞中gremlin的表达较低。Gremlin，也被称为v-mos下调；drm属于dan（神经母细胞瘤中差异筛选基因畸变）家族蛋白，被认为是BMP信号的拮抗剂。BMP-2对gremlin基因表达的下调具有时间依赖性和剂量依赖性。用格莱姆林处理C2C12细胞可抑制碱性磷酸酶诱导的BMP-2活性。综上所述，BMP-2抑制了C2C12细胞中gremlin的转录，这一机制可能在成骨细胞分化过程中增强了BMP的作用。

Bone morphogenetic protein-2 (BMP-2) stimulates osteoblast differentiation, but inhibits myogenetic differentiation in C2C12 myoblasts. To evaluate important genes for osteoblast differentiation induced by BMP-2, we performed a microarray analysis on C2C12 cells treated with or without BMP-2 for 4 days. We found that gremlin expression was lower in C2C12 cells treated with BMP-2 as compared to untreated cells. gremlin, also called downregulated by v-mos; drm belongs to dan (differential-screening selected gene aberrative in neuroblastoma) family protein, which is known as an antagonist of BMP signaling. Down-regulation of gremlin gene expression by BMP-2 occurred in both time- and dose-dependent manners. Treatment of C2C12 cells with gremlin prevented the alkaline phosphatase activity induced BMP-2. In conclusion, BMP-2 inhibited gremlin transcription in C2C12 cells, a mechanism that probably enhances BMP action during osteoblast differentiation.