Bone Morphogenetic Protein-2 Is a Regulator of Cell Adhesion

Abstract

Bone morphogenetic proteins (BMPs) are a group of peptide growth factors closely related to transforming growth factors-β. The BMPs are suggested to play an essential role in bone development and they are strong candidate molecules to be used clinically to improve fracture healing. BMPs are also involved in the differentiation of several other tissues during embryogenesis. Here, we show that human recombinant BMP-2 regulates cell–matrix interactions by modifying the expression of integrin-type receptors. The synthesis of α3 integrin was down-regulated by BMP-2 in two osteogenic sarcoma-derived cell lines, Saos-2 and HOS, and also in human fetal chondrocytes. BMP-2 had no effect on the expression of α1, α2, α5, α6, and αV integrins. BMP-2 reduced the expression of α3 integrin subunit at mRNA level. Laminin-5 was shown to be the ligand for α3β1 integrin on Saos cells and BMP-2 decreased the ability of Saos cells to attach to it. These results suggest that BMP-2 has a specific effect on the α3β1 integrin-mediated cell adhesion to laminin-5. Given the fact that BMP-2 is expressed in osteosarcomas, in addition to in bone, this mechanism is putatively important especially in bone development and tumors. We also studied the effect of BMP-2 on a human keratinocyte cell line, HaCaT. In HaCaT cells, the expression of α2 integrin was strongly down-regulated by BMP-2, whereas its effect on the expression of α3 integrin was smaller. We suggest that the effects of BMP-2 may be partially mediated by specifically altered cell adhesion.