Osteoprotegerin binding proteins and receptors

Abstract

A novel polypeptide, osteoprotegerin binding protein, involved in osteolcast maturation has been identified based upon its affinity for osteoprotegerin. Nucleic acid sequences encoding the polypeptide, or a fragment, analog or derivative thereof, vectors and host cells for production, methods of preparing osteoprotegerin binding protein, and binding assays are also described. Compositions and methods for the treatment of bone diseases such as osteoporosis, bone loss due to arthritis or metastasis, hypercalcemia, and Paget's disease are also provided. Receptors for osteoprotegerin binding proteins are also described. The receptors, and agonists and antagonists thereof, may be used to treat bone diseases.

1 - 42 . (canceled)  
     
     
         43 . A method for identifying a compound which decreases the activity of osteoprotegerin binding protein (OPGbp) comprising: adding to a cell culture a test compound under conditions where the cell culture forms osteoclasts in the presence of OPGbp; and measuring osteoclast formation, wherein a decrease in osteoclast formation in the presence of the test compound indicates that the compound decreases the activity of OPGbp.  
     
     
         44 . A method for identifying a compound which increases the activity of osteoprotegerin binding protein (OPGbp) comprising: adding to a cell culture a test compound under conditions where the cell culture forms osteoclasts in the presence of OPGbp; and measuring osteoclast formation, wherein an increase in osteoclast formation in the presence of the test compound indicates that the compound increases the activity of OPGbp.  
     
     
         45 . The method of claims  43  or  44  wherein the test compound binds to OPGbp.  
     
     
         46 . The method of claims  43  or  44  wherein the test compound binds to ODAR.  
     
     
         47 . The method of claims  43  or  44  wherein the test compound is an antibody or fragment thereof.  
     
     
         48 . The method of  claim 47  wherein the test compound is an antibody or fragment thereof which binds OPGbp.  
     
     
         49 . The method of  claim 47  wherein the test compound is an antibody or fragment thereof which binds ODAR.  
     
     
         50 . The method of claims  43  or  44  wherein the test compound is derived from human OPGbp.  
     
     
         51 . The method of claims  43  or  44  wherein the test compound is derived from human ODAR.  
     
     
         52 . The method of claims  43  or  44  wherein the test compound comprises part or all of the extracellular domain of human ODAR.  
     
     
         53 . The method of claims  43  or  44  wherein the test compound comprises part or all of the extracellular domain of human OPGbp.  
     
     
         54 . The method of claims  43  or  44  wherein OPGbp comprises the amino acid sequence from residues 1 to 317 inclusive as shown in SEQ ID NO:3 or a fragment thereof.  
     
     
         55 . The method of  claim 53  wherein the extracellular domain of human OPGbp comprises residues 69-317 inclusive as shown in SEQ ID NO:3 or a fragment thereof.  
     
     
         56 . The method of  claim 43  wherein the test compound increases bone density.  
     
     
         57 . The method of  claim 43  wherein the test compound decreases bone resorption.