BONE MORPHOGENETIC PROTEIN-2 IS A REGULATOR OF CELL-ADHESION

Bone morphogenetic proteins (BMPs) are a group of peptide growth facto rs closely related to transforming growth factors-beta. The BMPs are s uggested to play an essential role in bone development and they are st rong candidate molecules to be used clinically to improve fracture hea ling. BMPs are also involved in the differentiation of several other t issues during embryogenesis. Here, we show that human recombinant BMP- 2 regulates cell-matrix interactions by modifying the expression of in tegrin-type receptors. The synthesis of alpha 3 integrin was down-regu lated by BMP-2 in two osteogenic sarcoma-derived cell lines, Saos-a an d HOS, and also in human fetal chondrocytes. BMP-2 had no effect on th e expression of alpha 1, alpha 2, alpha 5, alpha 6, and alpha V integr ins. BMP-2 reduced the expression of alpha 3 integrin subunit at mRNA level. Laminin-5 was shown to be the Ligand for alpha 3 beta 1 integri n on Saos cells and BMP-2 decreased the ability of Saos cells to attac h to it. These results suggest that BMP-2 has a specific effect on the alpha 3 beta 1 integrin-mediated cell adhesion to laminin-5. Given th e fact that BMP-2 is expressed in osteosarcomas, in addition to in bon e, this mechanism is putatively important especially in bone developme nt and tumors. We also studied the effect of BMP-2 on a human keratino cyte cell line, HaCaT. In HaCaT cells, the expression of alpha 2 integ rin was strongly down-regulated by BMP-2, whereas its effect on the ex pression of alpha 3 integrin was smaller. We suggest that the effects of BMP-2 may be partially mediated by specifically altered cell adhesi on. (C) 1997 Academic Press.