Potent ectopic bone-inducing activity of bone morphogenetic protein-4/7 heterodimer

Biochem Biophys Res Commun. 1995 May 25;210(3):670-7. doi: 10.1006/bbrc.1995.1712.


We have purified and characterized recombinant Xenopus bone morphogenetic 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 formation in a dose-dependent manner. The xBMP-4/7 heterodimer showed the strongest activity, with an effective dose of 1-30 micrograms, while more than 10 micrograms of xBMP-4 or 7 homodimer was required for a significant effect. Histological examination revealed that xBMP-4/7 implants showed intramembranous 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 results suggest that the heterodimeric form of BMP would generate the strongest signal triggering osteogenic differentiation of osteoprogenitor cells in adult tissues.

MeSH terms

  • Alkaline Phosphatase / biosynthesis
  • Amino Acid Sequence
  • Animals
  • Bone Development / drug effects*
  • Bone Marrow Cells
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • Cell Differentiation / drug effects
  • Cell Line
  • Cells, Cultured
  • Consensus Sequence
  • Enzyme Induction
  • Growth Substances / pharmacology*
  • Kinetics
  • Male
  • Molecular Sequence Data
  • Osteoblasts / cytology*
  • Osteoblasts / drug effects
  • Protein Biosynthesis
  • Protein Multimerization
  • Proteins / isolation & purification
  • Proteins / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / pharmacology
  • Spodoptera
  • Transfection
  • Transforming Growth Factor beta*
  • Xenopus
  • Xenopus Proteins


  • Bmp7 protein, rat
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • Growth Substances
  • Proteins
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Xenopus Proteins
  • bmp7.1 protein, Xenopus
  • Alkaline Phosphatase