Methods of identifying obm modulators

Abstract

Novel proteins and polypeptides binding to osteoclastogenesis inhibitory factor (OCIF) (OCIF-binding molecules, OBMs) and nucleic acids encoding these proteins and polypeptides are provided. Processes for producing these proteins, polypeptides, and nucleic acid molecules by genetic engineering are provided. Medicinal compounds are provided which comprise proteins and nucleic acids according to the invention, as well as proteins which bind to OBM, including anti-OBM antibodies. These compounds may be used for the treatment of bone disease.

1 . (canceled) 
     
     
         2 . A method for identifying a substance that modifies one or more activities of OCIF-binding molecule (OBM), comprising:
 contacting cells expressing OBM with a test substance; and   measuring an OBM-associated activity to identify whether the test substance modifies one or more activities of OBM.   
     
     
         3 . The method of  claim 2 , wherein OBM is a human or mouse OBM. 
     
     
         4 . The method of  claim 3 , wherein OBM is a secreted-form OBM. 
     
     
         5 . The method of  claim 2 , wherein OBM comprises the amino acid sequence of SEQ ID NO: 11, SEQ ID NO: 17 or SEQ ID NO: 19. 
     
     
         6 . The method of  claim 2 , wherein the OBM-associated activity is osteoclast formation or bone resorption. 
     
     
         7 . The method of  claim 2 , wherein the cells comprise mononuclear leukocytes. 
     
     
         8 . The method of  claim 2 , wherein the cells comprise osteoblastic stromal cells, preadipocyte cells, spleen cells, or a combination thereof. 
     
     
         9 . The method of  claim 8 , wherein the osteoblastic stromal cells are human or mouse osteoblastic stromal cells. 
     
     
         10 . The method of  claim 9 , wherein the mouse osteoblastic stromal cells are ST2 cells. 
     
     
         11 . The method of  claim 2 , wherein the cells are cultured in the presence of one or more osteotropic factors. 
     
     
         12 . The method of  claim 11 , wherein the one or more osteotropic factors are selected from the group consisting of active-form vitamin D 3 , parathyroid hormone (PTH), interleukin-1, interleukin-6, interleukin-11, Oncostatin M, and leukemia inhibitory factor. 
     
     
         13 . The method of  claim 11 , wherein the one or more osteotropic factors are active-form vitamin D 3  or PTH. 
     
     
         14 . The method of  claim 2 , wherein the measuring of the OBM-associated activity comprises detecting tartaric acid resistant acid phosphatase (TRAP) activity. 
     
     
         15 . The method of  claim 2 , wherein the measuring of the OBM-associated activity comprises detecting the presence of vitronectin receptors. 
     
     
         16 . The method of  claim 2 , wherein the test substance inhibits one or more activities of the OBM. 
     
     
         17 . The method of  claim 16 , wherein the inhibition of OBM by the test substance is identified by decreased osteoclast formation in the presence of the test substance as compared to the absence of the test substance. 
     
     
         18 . The method of  claim 2 , wherein the test substance increases one or more activities of the OBM. 
     
     
         19 . The method of  claim 18 , wherein the increased activity of OBM by the test substance is identified by increased osteoclast formation in the presence of the test substance as compared to the absence of the test substance. 
     
     
         20 . The method of  claim 2 , further comprising determining whether said substance binds to OBM. 
     
     
         21 . A method for identifying a modulator of OCIF-binding molecule (OBM), comprising:
 contacting an OBM with one or more test substances; and   measuring the specific binding between the one or more test substances and the OBM to identify whether the test substance is a modulator of OBM.   
     
     
         22 . The method of  claim 21 , wherein the method comprises screening a peptide library.