POTENT ECTOPIC BONE-INDUCING ACTIVITY OF BONE MORPHOGENETIC PROTEIN-47 HETERODIMER/

We have purified and characterized recombinant Xenopus bone morphogene tic proteins (xBMPs): homodimers of xBMP-4, 7 and heterodimers (xBMP-4 /7) produced by a baculovirus expression system. Highly purified xBMPs had homogeneous NH2-termini predicted from a consensus motif, Arg-X-X -Arg, while they possessed diverse sugar chains. Implantation of xBMPs together with pure collagen carrier in rats induced new bone formatio n in a dose-dependent manner. The xBMP-4/7 heterodimer showed the stro ngest activity, with an effective dose of 1-30 mu g, while more than 1 0 mu g of xBMP-4 or 7 homodimer was required for a significant effect. Histological examination revealed that xBMP-4/7 implants showed intra membranous ossification without chondrogenesis. In primary cultures of rat bone marrow stromal cells, xBMP-4/7 induced alkaline phosphatase 3-fold more strongly than xBMP-7 and 20-fold more than xBMP-4. These r esults suggest that the heterodimeric form of BMP would generate the s trongest signal triggering osteogenic differentiation of osteoprogenit or cells in adult tissues. (C) 1995 Academic Press, Inc.