Cell calcification supressing proteins, and genes of the proteins

Abstract

This invention provides cell-calcification inhibitory proteins as well as genes encoding the proteins. Based on the discovery of a novel isoform gene of the c-erg gene (herein referred to as “C-11 gene”) which is an erg gene derived from chickens, the nucleotide sequence of the gene has been determined, and then the expression of a protein encoded by such gene (herein referred to as “C-11 protein”) has been confirmed. Further, it has been discovered that when the c-erg or C-11 gene is introduced into osteoblasts, the calcification of the cells is inhibited.

What is claimed is:  
     
         1 . A C-11 protein comprising a protein selected from the group consisting of: 
 (a) a protein comprising an amino acid sequence having SEQ ID NO. 2 (SEQUENCE LISTING); and    (b) a protein comprising an amino acid sequence that is derived from the amino acid sequence having SEQ ID NO. 2 by deletion, substitution or insertion of one or more amino acids, said protein having cell-calcification inhibitory activity.    
     
     
         2 . A gene encoding the protein according to  claim 1 .  
     
     
         3 . A pharmaceutical composition comprising the protein according to  claim 1 .  
     
     
         4 . The pharmaceutical composition according to  claim 3 , wherein said composition is intended for a cell-calcification inhibitor.  
     
     
         5 . A cell-calcification inhibitor comprising a c-erg protein selected from the group consisting of: 
 (a) a protein comprising an amino acid sequence having SEQ ID NO. 4 (SEQUENCE LISTING); and    (b) a protein comprising an amino acid sequence that is derived from the amino acid sequence having SEQ ID NO. 4 by deletion, substitution or insertion of one or more amino acids, said protein having cell-calcification inhibitory activity.    
     
     
         6 . An antibody to the C-11 protein according to  claim 1 .  
     
     
         7 . The antibody according to  claim 6 , wherein said antibody is a monoclonal antibody.  
     
     
         8 . A method for measuring the calcification of cells comprising: 
 measuring the expression of a C-11 gene or a c-erg gene in the cells.    
     
     
         9 . The method according to  claim 8 , wherein the expression of the gene is measured by the amount of C-11 mRNA expressed in the cells or the amount of c-erg mRNA expressed in the cells using a probe against a DNA sequence specific to the C-11 gene or to the c-erg gene.  
     
     
         10 . The method according to  claim 8 , wherein the expression of the gene is measured by the amount of expression of a C-11 protein in the cells or the amount of expression of a c-erg protein in the cells.  
     
     
         11 . The method according to  claim 8 , wherein the expression of the gene is measured by the amount of the C-11 protein expressed in the cells or the amount of the c-erg protein expressed in the cells by means of the antibody according to claims  6 , or  7 .  
     
     
         12 . A method for diagnosing osteoarthritis or OPLL comprising: 
 measuring the cell-calcification using a method according to any of claims  8 - 11 .    
     
     
         13 . A kit for measuring the cell-calcification of cells comprising either or both of an antibody to a C-11 protein and an antibody to a c-erg protein.  
     
     
         14 . A method for screening a substance having cell-calcification inhibitory blocking activity, said method comprising using cells transformed with a gene encoding a protein selected from the group consisting of: 
 (a) a protein comprising an amino acid sequence having SEQ ID NO. 2 (SEQUENCE LISTING);    (b) a protein comprising an amino acid sequence that is derived from the amino acid sequence having SEQ ID NO. 2 by deletion, substitution or insertion of one or more amino acids, said protein having cell-calcification inhibitory activity;    (c) a protein comprising an amino acid sequence having SEQ ID NO. 4. (SEQUENCE LISTING); and    (d) a protein comprising an amino acid sequence that is derived from the amino acid sequence having SEQ ID NO. 4 by deletion, substitution or insertion of one or more amino acids, said protein having cell-calcification inhibitory activity.    
     
     
         15 . A pharmaceutical composition comprising an erg protein.  
     
     
         16 . A pharmaceutical composition comprising an erg gene.  
     
     
         17 . A pharmaceutical composition comprising a C-11 protein or a c-erg protein.  
     
     
         18 . A pharmaceutical composition comprising a C-11 gene or a c-erg gene.  
     
     
         19 . A pharmaceutical composition comprising a protein having a consensus amino acid sequence between a c-erg protein and a C-11 protein.