Human extracellular matrix-1

Abstract

A human ECM-1 polypeptide and DNA (RNA) encoding such polypeptide and a procedure for producing such polypeptide by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptide for stimulating the differentiation in growth of osteoblasts and osteoclasts, which may be used to promote the healing of bone fractures and de novo bone formation, for osteoporosis, for and to promote angiogenesis. Antagonists to the polypeptide of the present invention are also disclosed which may be utilized to treat osteodystrophy, osteohypertrophy, osteoma, osteoblastoma and cancers. Diagnostic assays for identifying mutations in nucleic acid sequence encoding a polypeptide of the present invention.

1 . An isolated polynucleotide comprising a member selected from the group consisting of: 
 (a) a polynucleotide having at least 95% identity to a polynucleotide encoding a polypeptide comprising an amino acid sequence set forth in FIGS.  1 A-F;    (b) a polynucleotide having at least 95% identity to a polynucleotide encoding a polypeptide comprising amino acids 20 to 540 of FIGS.  1 A-F;    (c) a polynucleotide having at least 95% identity to a polynucleotide encoding a polypeptide comprising the hECM-1-SV1 amino acid sequence; and    (d) a polynucleotide which is complementary to the polynucleotide of (a), (b) or (c).    
     
     
         2 . The polynucleotide of  claim 1  wherein the polynucleotide is DNA.  
     
     
         3 . The polynucleotide of  claim 1  wherein the polynucleotide is RNA.  
     
     
         4 . The polynucleotide of  claim 2  encoding a polypeptide comprising amino acids 20 to 540 set forth in FIGS.  1 A-F.  
     
     
         5 . The polynucleotide of  claim 2  comprising nucleotides 139 to 1701 set forth in FIGS.  1 A-F.  
     
     
         6 . The polynucleotide of  claim 2  comprising nucleotides 139 to 1701 but missing nucleotides 812 to 1186 as set forth in FIGS.  1 A-F.  
     
     
         7 . An isolated polynucleotide comprising a member selected from the group consisting of: 
 (a) a polynucleotide having at least 95% identity to a polynucleotide encoding the same mature polypeptide expressed by the DNA contained in ATCC Deposit No. 97302; and    (b) a polynucleotide complementary to the polynucleotide of (a).    
     
     
         8 . A vector comprising the DNA of  claim 2 .  
     
     
         9 . A host cell comprising the vector of  claim 8 .  
     
     
         10 . A process for producing a polypeptide comprising: expressing from the host cell of  claim 9  the polypeptide encoded by said DNA.  
     
     
         11 . A process for producing cells capable of expressing a polypeptide comprising genetically engineering cells with the vector of  claim 8 .  
     
     
         12 . A polypeptide comprising a member selected from the group consisting of: 
 (a) a polypeptide having an amino acid sequence set forth in FIGS.  1 A-F;    (b) a polypeptide comprising amino acids 20 to 540 set forth in FIGS.  1 A-F;    (c) a polypeptide which is at least 95% identical to the polypeptide of (a); and    (d) a polypeptide which is at least 95% identical to the polypeptide of (b).    
     
     
         13 . The polypeptide of  claim 12  comprising amino acid 20 to amino acid 540 of FIGS.  1 A-F.  
     
     
         14 . An antibody against the polypeptide of  claim 12 .  
     
     
         15 . An agonist to the polypeptide of  claim 12 .  
     
     
         16 . An antagonist to the polypeptide of  claim 12 .  
     
     
         17 . A method for the treatment of a patient having need of hECM-1 comprising: administering to the patient a therapeutically effective amount of the polypeptide of  claim 12 .  
     
     
         18 . A process for diagnosing a disease or a susceptibility to a disease comprising: 
 determining a mutation in the polynucleotide of  claim 1 .    
     
     
         19 . A diagnostic process comprising: 
 analyzing for the presence of the polypeptide of  claim 12  in a sample derived from host.    
     
     
         20 . A method of stimulating angiogenesis in a patient comprising administering to the patient the polypeptide of  claim 16.