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

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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.