Compositions and methods for treating bone conditions

Abstract

A method of treating a degenerative bone condition of a subject includes administering to hematopoietic progenitor cells or osteoclast progenitor cells of the subject at least one agent that substantially reduces the interaction of at least one of C3a or C5a with the C3a receptor (C3aR) and/or C5a receptor (C5aR), a STAT3/IL-6 signaling pathway antagonist, and a combination thereof, the agent being administered to the hematopoietic progenitor cells or osteoclast progenitor cells at an amount effective to inhibit osteoclast differentiation of hematopoietic progenitor cells or osteoclast progenitor cells.

Having described the invention, we claim: 
     
         1 . A method of treating a degenerative bone condition, the method comprising:
 administering to hematopoietic progenitor cells or osteoclast progenitor cells of the subject at least one agent that substantially reduces the interaction of at least one of C3a or C5a with the C3a receptor (C3aR) and/or C5a receptor (C5aR), a STAT3/IL-6 signaling pathway antagonist, and a combination thereof, the agent being administered to the hematopoietic progenitor cells or osteoclast progenitor cells at an amount effective to inhibit osteoclast differentiation of hematopoietic progenitor cells or osteoclast progenitor cells.   
     
     
         2 . The method of  claim 1 , the agent comprising at least one complement antagonist selected from the group consisting of a small molecule, a polypeptide, and a polynucleotide. 
     
     
         3 . The method of  claim 2 , the at least one complement antagonist selected from the group consisting of DAF or an antibody directed against at least one of C3, C5, C3 convertase, C5 convertase, C3a, C5a, C3aR, or C5aR. 
     
     
         4 . The method of  claim 2 , the polynucleotide comprising a small interfering RNA directed against a polynucleotide encoding at least one of C3, C5, C3aR, or C5aR. 
     
     
         5 . The method of  claim 3 , the at least one complement antagonist including an antibody directed against C5aR and an antibody directed against C3aR. 
     
     
         6 . The method of  claim 3 , the at least one complement antagonist including an antibody directed against C5a and an antibody directed against C3a. 
     
     
         7 . The method of  claim 3 , the at least one complement antagonist including an antibody directed against C5 and an antibody directed against C3. 
     
     
         8 . The method of  claim 1 , the agent being administered to the hematopoietic progenitor cells or osteoclast progenitor cells in vitro. 
     
     
         9 . The method of  claim 1 , the agent being administered locally to the hematopoietic progenitor cells or osteoclast progenitor cells at the site of the bone condition. 
     
     
         10 . The method of  claim 1 , the agent being conjugated to a targeting moiety that targets hematopoietic progenitor cells or osteoclast progenitor cells. 
     
     
         11 . The method of  claim 1  wherein the bone condition comprises osteopenia or osteoporosis. 
     
     
         12 . A method of treating post-menopausal osteoporosis, the method comprising:
 administering to hematopoietic progenitor cells or osteoclast progenitor cells of the subject at least one complement antagonist that substantially reduces the interaction of at least one of C3a or C5a with the C3a receptor (C3aR) and/or C5a receptor (C5aR), the agent being administered to the hematopoietic progenitor cells or osteoclast progenitor cells at an amount effective to inhibit osteoclast differentiation of hematopoietic progenitor cells.   
     
     
         13 . The method of  claim 12 , the at least one complement antagonist selected from the group consisting of DAF or an antibody directed against at least one of C3, C5, C3 convertase, C5 convertase, C3a, C5a, C3aR, or C5aR. 
     
     
         14 . The method of  claim 12 , the at least one complement antagonist including an antibody directed against C5aR and an antibody directed against C3aR or an antibody directed against C5a and an antibody directed against C3a. 
     
     
         15 . The method of  claim 12 , the agent being administered to the hematopoietic progenitor cells or osteoclast progenitor cells in vitro. 
     
     
         16 . The method of  claim 12 , the agent being administered locally to the hematopoietic progenitor cells or osteoclast progenitor cells of the bone marrow. 
     
     
         17 . The method of  claim 12 , the agent being conjugated to a targeting moiety that targets hematopoietic progenitor cells or osteoclast progenitor cells of the bone marrow. 
     
     
         18 . A method of treating post-menopausal osteoporosis of a subject, the method comprising:
 administering locally to bone marrow of the subject at least one complement antagonist that substantially reduces the interaction of at least one of C3a or C5a with the C3a receptor (C3aR) and C5a receptor (C5aR), the agent being administered locally to the bone marrow cells of the subject at an amount effective to inhibit osteoclast differentiation of hematopoietic progenitor cells or osteoclast progenitor cells.   
     
     
         19 . The method of  claim 18 , the at least one complement antagonist selected from the group consisting of DAF or an antibody directed against at least one of C3, C5, C3 convertase, C5 convertase, C3a, C5a, C3aR, or C5aR. 
     
     
         20 . The method of  claim 19 , the at least one complement antagonist including an antibody directed against C5aR and an antibody directed against C3aR or an antibody directed against C5a and an antibody directed against C3a.