Background Bone morphogenetic proteins (BMPs) are members of the transforming growth factor- superfamily of growth factor. BMPs participate in regulation of angiogenesis, cell communication and signal transduction during differentiation. Object To investigate the gene expression profiles that contribute to angiogenic, cell communication and signal transduction during osteoblastic differentiation in mesenchyma stem cells by BMP-2 treatment. Methods D1 cells (mouse mesenchymal stem cells) were cultured in osteogenic differentiation medium (ODM) for 3 days, and then treated with BMP-2 for 24 hr. Total RNA was extracted using Trizol, purified using RNeasy columns. Total RNA was amplified and purified using the Ambion Illumina RNA amplification kit to yield biotinylated cRNA. The data analysis up- and down-regulation gene expression folds in angiogenesis, cell communication and signal transduction. Results Ptgis (prostaglandin synthase mRNA) was increased 1.65 folds than control. Fmod (fibromodulin mRNA), Ctgf (connective tissue growth factor mRNA), Prelp (proline arginine-rich end leucine-rich repeat mRNA), Cyr61 (cysteine rich protein61 mRNA) and Il1rn (IL1 receptor antagonist transcript variant 1 mRNA) were increased 3.19, 3.06, 2.58, 2.03 and 2.01 folds, respectively. Gas6 (growth arrest specific6 mRNA), Ptprk (protein tyrosine phosphatase receptor type K mRNA), Flrt3 (fibronectin leucine rich transmembrane protein3 mRNA) and Rab3d (member RAS oncogene family mRNA) were increased 2.08, 1.58, 1.58 and 1.73 folds, respectively. Hp (haptoglobin mRNA; blood circulation) was decreased -1.62 fold than control. Chrnb1 (cholinergic receptor, nicotinic, beta polypeptide 1 mRNA) and Selp (selectin, platelet mRNA) were decreased -1.68 and -1.87 folds, respectively. Il1rl1 (IL 1 receptor-like 1 transcript variant2 mRNA) was decreased -1.55 fold. Conclusion We demonstrate expression of genes during osteoblastic differentiation that were involved angiogenic, cell communication and signal transduction genes modulation to enhanced differentiation in MSC by BMP-2. Furthermore, these data should facilitate the informed use of BMP-2 as a therapeutic agent and tissue engineering tool.