OBJECTIVESTo examine the gene expression profile of bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF) during entochondrostosis of mice and explore the expression rules and effects between BMP-2 and VEGF, and to detect the expression of VEGF in BMP-2 induced entochondrostosis in vivo.

METHODScDNA microarray technique with 34,000 genes was used to analyze the gene expression profiles during entochondrostosis in the limbs of mice embryo from E10 to E14. Pathway analysis of BMP-2 and VEGF was performed with GCOS1.2 software. An experimental model of femoral muscular pouch in 20 mice was adopted. The expression of VEGF was examined by in situ hybridization method and immunohistochemical method in BMP-2 induced entochondrostosis in vivo.

RESULTSThe expression signals of VEGF mRNA and VEGF appeared in cytoplasm during condensation of mesenchymal cell. As the mesenchymal cells differentiated into precartilage, the expression signals decreased in mesenchymal cells, but increased in chondrocytes and kept getting denser in the process of cartilage maturity. The peak expression of VEGF mRNA and VEGF in the experimental group appeared on the 14th day, accompanied by numerous hypertrophic chondrocytes. When mature cartilage calcified and new bone trabecula formed, the expression of VEGF mRNA and VEGF decreased in chondrocytes, but still expressed moderately in the osteoblasts and osteocytes.

CONCLUSIONSThe finding reveals a complex pattern of gene coexpression of BMP-2 and VEGF during the critical period of entochondrostosis. It's feasible for the clinical application of BMP-2 in orthopedics.