Nell-1 enhanced bone mineralization

Abstract

This invention pertains to the discovery that the human NELL-1 gene induces or upregulates bone mineralization. The NELL-1 gene or gene product thus provides a convenient target for screening for modulators of bone mineralization. In addition, NELL-1 can be used to facilitate repair of bone fractures and/or to generally increase bone density.

1 . A method of facilitating the repair of bone fractures, the method comprising increasing concentration of a NELL-1 gene product at or near the fracture site. 
     
     
         2 . The method of  claim 1 , where the NELL-1 gene product is increased in an osteogenic or bone precursor cell present at or near the fracture site. 
     
     
         3 . The method of  claim 1 , comprising introducing an osteogenic cell or bone precursor cell that overexpresses NELL-1 into the fracture site. 
     
     
         4 . The method of  claim 2 , comprising increasing the concentration of a NELL-1 gene product in the osteogenic cell or the bone precursor cell in situ 
     
     
         5 . The method of  claim 2 , wherein the increasing the concentration of NELL-1 gene product comprises upregulating expression of a NELL-1 gene in the osteogenic cell. 
     
     
         6 . The method of  claim 2 , wherein the upregulating comprises upregulating expression of an endogenous NELL-1 gene in the osteogenic cell. 
     
     
         7 . The method of  claim 5 , wherein the upregulating comprises transfecting the cell with a vector that expresses a NELL-1 protein. 
     
     
         8 . The method of  claim 7 , wherein the vector constitutively expresses a NELL-1 protein. 
     
     
         9 . The method of  claim 7 , wherein expression of a NELL-1 protein by the vector is inducible. 
     
     
         10 . The method of  claim 1 , wherein the increasing the concentration of NELL-1 gene product comprises contacting the cell with a NELL-1 polypeptide. 
     
     
         11 . The method of  claim 2 , wherein the osteogenic cell is selected from the group consisting of a mature osteoblast, osteoblast, a mesenchymal cell, a fibroblast cell, a fetal embryonic cells, a stem cells, a bone marrow cell, a dura cell, a chrondrocyte, and a chondroblast. 
     
     
         12 . The method of  claim 1 , wherein the NELL-peptide is encoded by a sequence of SEQ ID NO: 1 or SEQ ID NO: 2. 
     
     
         13 . A method of facilitating the repair of a bone fracture, the method comprising contacting the bone fracture site with a NELL-1 protein. 
     
     
         14 . The method of  claim 13 , wherein the NELL-1 protein is combined with a collagen. 
     
     
         15 . The method of  claim 13 , wherein the NELL-peptide is encoded by a sequence of SEQ ID NO: 1 or SEQ ID NO: 2.