Bmp-alk3 antagonists and uses for promoting bone growth

Abstract

In certain aspects, the present invention provides compositions and methods for promoting bone growth and increasing bone density and strength. In certain embodiments, the present invention provides ALK3 polypeptides, including ALK3-Fc fusion proteins.

We claim: 
     
         1 . An isolated polynucleotide comprising a coding sequence for a polypeptide comprising the amino acid sequence of SEQ ID NO:7. 
     
     
         2 . The isolated polynucleotide of  claim 1 , wherein the isolated polynucleotide comprises a sequence of SEQ ID NO: 12. 
     
     
         3 . A recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide of  claim 1 . 
     
     
         4 . A cell transformed with a recombinant polynucleotide of  claim 1 . 
     
     
         5 . The cell of  claim 4 , wherein the cell is a mammalian cell. 
     
     
         6 . The cell of  claim 5 , wherein the cell is a CHO cell or a human cell. 
     
     
         7 . A method for promoting bone growth, increasing bone density or increasing bone strength, the method comprising administering to a subject an effective amount of a BMP or ALK3 antagonist selected from the group consisting of:
 a) a polypeptide comprising an amino acid sequence at least 90% identical to SEQ ID NO: 3;   b) a polypeptide comprising at least 50 consecutive amino acids selected from SEQ ID NO: 3;   c) an antibody that binds to BMP2 and inhibits the interaction between BMP2 and ALK3;   d) an antibody that binds to BMP4 and inhibits the interaction between BMP4 and ALK3; and   e) an antibody that binds to ALK3 and inhibits the interaction between ALK3 and one or more ligands of ALK3.