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C2 C12成肌细胞的成肌分化。为了评估BMP-2诱导成骨细胞分化的重要基因，我们对用或不用BMP-2处理4天的C2 C12细胞进行了微阵列分析。我们发现，与未处理的细胞相比，在用BMP-2处理的C2 C12细胞中gremlin表达较低。gremlin，也称为v-mos下调蛋白; drm属于dan（神经母细胞瘤差异筛选选择基因变异）家族蛋白，被称为BMP信号传导的拮抗剂。BMP-2对gremlin基因表达的下调具有时间和剂量依赖性。用gremlin处理C2 C12细胞可抑制BMP-2诱导的碱性磷酸酶活性。总之，BMP-2抑制了C2 C12细胞中的gremlin转录，这一机制可能增强了BMP在成骨细胞分化过程中的作用。

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.