Controlling osteogenesis by inhibition of osteogenic suppressors

Abstract

The present invention provides methods of screening for agents that inhibit the activity or expression of one or more polypeptides that contribute to the suppression of osteogenesis. The invention also provides methods of inducing osteogenesis in a cell by administering to the cell an agent that inhibits one or more polypeptides that contribute to the suppression of osteogenesis.

1 . A method for identifying agents that promote osteogenesis, the methods comprising,
 (a) contacting a plurality of agents to at least one of the polypeptides selected from Table 1;   (b) measuring the activity of at least one of the polypeptides;   (c) selecting at least one of the plurality of agents, wherein the selected agent(s) inhibit the activity of at least one of the polypeptides; and   (d) measuring the ability of the selected agent(s) to promote osteogenesis, thereby identifying agents that promote osteogenesis.   
     
     
         2 . The method of  claim 1 , wherein the polypeptides are expressed in a host cell. 
     
     
         3 . The method of  claim 2 , wherein the measuring step (b) comprises measuring the expression of the at least one polypeptides. 
     
     
         4 . The method of  claim 3 , wherein measuring the expression comprises measuring the level of transcription. 
     
     
         5 . The method of  claim 2 , wherein the cells are mammalian cells. 
     
     
         6 . The method of  claim 1 , wherein the measuring step (d) is carried out in vitro. 
     
     
         7 . The method of  claim 1 , wherein the measuring step (d) is carried out in vivo. 
     
     
         8 . A method for promoting osteogenesis in a mammalian cell, the method comprising contacting the cell with an siRNA that inhibits expression of at least one of the gene products selected from Table 1. 
     
     
         9 . The method of  claim 8 , wherein the cell is a stem cell. 
     
     
         10 . The method of  claim 9 , wherein the stem cell is a mesenchymal stem cell. 
     
     
         11 . A method for promoting osteogenesis in a mammalian cell, the method comprising contacting a cell with an agent that inhibits the activity of a polypeptide selected from Table 1. 
     
     
         12 . The method of  claim 11 , wherein the cell is a stem cell. 
     
     
         13 . The method of  claim 12 , wherein the stem cell is a mesenchymal stem cell.