Methods compositions and article of manufacture for modulating bone growth

Abstract

Novel methods and pharmaceutical compositions suitable for modulating bone growth and remodeling, preventing bone diseases, inducing bone growth or repair by cannabinoid receptor-mediated effects on bone cells is disclosed. Methods of identifying bone growth modulating agents are also disclosed.

1 . A method of identifying a bone growth modulating agent, comprising screening a plurality of molecules to thereby uncover a molecule capable of regulating an expression or activity of at least one cannabinoid receptor, said molecule being the bone growth modulating agent. 
     
     
         2 . The method of  claim 1 , further comprising determining an ability of said molecule to modify bone formation rate and/or altering bone mineralization perimeter. 
     
     
         3 . The method of  claim 1 , wherein said screening is effected by exposing bone cells to said plurality of molecules and determining said expression of said at least one cannabinoid receptor in said bone cells. 
     
     
         4 . The method of  claim 1 , wherein said cannabinoid receptor is selected from the group consisting of a CB1 receptor, a CB1-like receptor, a CB2 receptor, a CB2-like receptor, and a non-CB1 non-CB2 receptor. 
     
     
         5 . The method of  claim 1 , wherein said at least one cannabinoid receptor is a bone cell or bone cell progenitor cannabinoid receptor. 
     
     
         6 . The method of  claim 5 , wherein said bone cell progenitor is an osteogenic cell. 
     
     
         7 . The method of  claim 5 , wherein said bone cell progenitor is a stromal cell. 
     
     
         8 . The method of  claim 5 , wherein said bone cell progenitor is a bone resorbing cell progenitor. 
     
     
         9 . The method of  claim 3 , wherein said bone cell is a cultured bone cell. 
     
     
         10 . The method of  claim 5 , further comprising exposing said bone cells to an osteoclast differentiating factor. 
     
     
         11 . The method of  claim 1 , wherein said expression of said cannabinoid receptor is determined by RT-PCR. 
     
     
         12 . A method of identifying and producing a pharmaceutical composition for modulating bone growth, comprising screening a plurality of molecules to thereby uncover a molecule capable of regulating an expression or activity of at least one cannabinoid receptor, said molecule being the bone growth modulating agent, and producing a pharmaceutical composition comprising said bone growth modulating agent and a pharmaceutically acceptable carrier. 
     
     
         13 . The method of  claim 12 , wherein said screening is effected by exposing bone cells to said plurality of molecules and determining said expression of said at least one cannabinoid receptor in said bone cells. 
     
     
         14 . The method of  claim 12 , wherein said cannabinoid receptor is selected from the group consisting of a CB1 receptor, a CB1-like receptor, a CB2 receptor, a CB2-like receptor, and a non-CB1 non-CB2 receptor. 
     
     
         15 . The method of  claim 12 , wherein said at least one cannabinoid receptor is a bone cell or bone cell progenitor cannabinoid receptor. 
     
     
         16 . The method of  claim 15 , wherein said bone cell progenitor is an osteogenic cell. 
     
     
         17 . The method of  claim 15 , wherein said bone cell progenitor is a stromal cell. 
     
     
         18 . The method of  claim 15 , wherein said bone cell progenitor is a bone resorbing cell progenitor. 
     
     
         19 . The method of  claim 13 , wherein said bone cell is a cultured bone cell. 
     
     
         20 . The method of  claim 12 , wherein said expression of said cannabinoid receptor is determined by RT-PCR.