SUBTLE DIFFERENCES IN THE MITOGENIC EFFECTS OF RECOMBINANT HUMAN BONEMORPHOGENETIC PROTEIN-2 TO PROTEIN-7 ON DNA-SYNTHESIS ON PRIMARY BONE-FORMING CELLS AND IDENTIFICATION OF BMP-2 4 RECEPTOR/

wThe bone morphogenetic proteins (BMPs) are a group of related protein s capable of inducing the formation of new cartilage and bone. We repo rt here a direct comparison of members of the BMP family in their capa bility to induce DNA synthesis in bone cell cultures. The promotion of DNA synthesis was determined in periosteal cells and epiphyseal and s ternal chondrocytes of embryonic chick. We demonstrate that structural ly homologous BMP-2 and BMP-4 exhibit the highest specific activity in the three tested cell types, whereas BMP-5, BMP-6 activity is moderat ely reduced in periosteal cells and highly reduced in epiphyseal and s ternal chondrocytes. The specific activity of BMP-7 is the lowest in t he three tested cell cultures. Receptor binding characteristics demons trate a binding of BMP-2 with high affinity (K-D = 0.45 nM) on periost eal cells, and excess of TGF-beta 1 does not displace BMP-4 binding. C hemical cross-linking with iodinated BMP-2 generates an affinity compl ex of 90 kDa. These findings suggest the presence of a BMP-2/BMP-4 rec eptor that discriminates subtle differences in function among homologo us members of the BMP family.