Estrogen Related Receptor, ERRalpha, A Regulator of Bone Formation

Abstract

Methods and pharmaceutical compositions are provided for modulating bone formation in a mammal. Methods are also provided for screening compounds for their efficacy as modulators of bone formation.

1 . A method of increasing proliferation or differentiation of osteoblasts in a mammal comprising administering to the mammal an effective amount of an agent selected from the group consisting of:
 (a) an estrogen related receptor alpha (ERRα) agonist;   (b) a substantially purified ERRα protein;   (c) a nucleotide sequence encoding ERRα protein; and   (d) an agent which enhances expression of a gene encoding an ERRα protein.   
     
     
         2 . (canceled) 
     
     
         3 . A method of reducing proliferation or differentiation of osteoblasts in a mammal comprising administering to the mammal an effective amount of an agent selected from the group consisting of:
 (a) an ERRα antagonist;   (b) a purified antibody which binds specifically to an ERRα protein;   (c) an antisense nucleotide sequence complementary to and capable of hybridizing to a nucleotide sequence encoding an ERRα protein; and   (d) an agent which reduces expression of a gene encoding an ERRα protein.   
     
     
         4 . (canceled) 
     
     
         5 . The method of  claim 1 , for treating a disorder associated with bone loss. 
     
     
         6 . The method of  claim 5  wherein the disorder is selected from the group consisting of osteoporosis, osteoathritis, Paget's disease, periodontal disease, osteolytic bone tumour metastases in, for example, breast cancer and multiple myeloma, osteochondrodysplasias, osteogenesis imperfecta, sclerosing bone displasias and osteomalacia. 
     
     
         7 . The method of  claim 3 , for treating a disorder associated with unwanted bone formation. 
     
     
         8 . The method of  claim 7  wherein the disorder is selected from the group consisting of fibrodysplasia ossificans progressiva, osteoblastic bone metastases such as prostate cancer and osteosarcomas. 
     
     
         9 . The method of  claim 1  wherein the mammal is a human. 
     
     
         10 - 15 . (canceled) 
     
     
         16 . The method of  claim 1 , for increasing proliferation of osteoblasts. 
     
     
         17 . The method of  claim 1 , for increasing differentiation of osteoblasts. 
     
     
         18 . The method of  claim 3 , for reducing proliferation of osteoblasts. 
     
     
         19 . The method of  claim 3 , for reducing differentiation of osteoblasts. 
     
     
         20 . The method of  claim 3 , wherein the mammal is a human.