Promoter For Hard Tissue Formation

Abstract

The present invention provides an agent which induces acceleration of hard tissue formation, acceleration of cell differentiation and increase in cellular alkaline phosphatase activity, by directly acting on the cell. Specifically, it provides a hard tissue formation promoter, a cell differentiation inducer and a cellular alkaline phosphatase activity reinforcing agent comprising, as an active ingredient, a glycosaminoglycan or a salt thereof that keeps sulfate group and has the characteristics of the following (1) and (2): (1) a basic structure is a disaccharide repeating structure consisting of a hexuronic acid residue and a glucosamine residue, (2) one or less of the position among a 2-position hydroxyl group of a hexuronic acid residue, a 6-position hydroxyl group of a glucosamine residue and a 2-position amino group of the glucosamine residue in the basic structure of the aforementioned (1) does not have the sulfate group. In this connection, it is preferable that the hexuronic acid residue is a glucuronic acid residue or an iduronic acid residue.

1 . A hard tissue formation promoter comprising, as an active ingredient, a glycosaminoglycan or a salt thereof which has a sulfate group and characteristics of the following (1) and (2):
 (1) a basic structure is a disaccharide repeating structure consisting of a hexuronic acid residue and a glucosamine residue,   (2) one or less of the position among a 2-position hydroxyl group of the hexuronic acid residue, a 6-position hydroxyl group of the glucosamine residue and a 2-position amino group of the glucosamine residue in the basic structure of the aforementioned (1) does not have the sulfate group.   
   
   
       2 . The hard tissue formation promoter according to  claim 1 , wherein the hexuronic acid residue is a glucuronic acid residue or an iduronic acid residue. 
   
   
       3 . The hard tissue formation promoter according to  claim 1  or  2 , wherein the glycosaminoglycan which has sulfate group and the aforementioned characteristics (1) and (2) is 1 or 2 or more substances selected from a group consisting of heparin, a substance which does not have the sulfate group on the 2-position hydroxyl group of the hexuronic acid residue of a heparin, a substance which does not have the sulfate group on the 6-position hydroxyl group of the glucosamine residue of the heparin and a substance which does not have the sulfate group on the 2-position amino group of the glucosamine residue of the heparin. 
   
   
       4 . The hard tissue formation promoter according to  claim 1 , wherein the hard tissue is a bone. 
   
   
       5 . A cell differentiation promoter comprising, as an active ingredient, a glycosaminoglycan or a salt thereof which has a sulfate group and has characteristics of the following (1) and (2):
 (1) a basic structure is a disaccharide repeating structure consisting of a hexuronic acid residue and a glucosamine residue,   (2) one or less of the position among a 2-position hydroxyl group of the hexuronic acid residue, a 6-position hydroxyl group of the glucosamine residue and a 2-position amino group of the glucosamine residue in the basic structure of the aforementioned (1) does not have the sulfate group.   
   
   
       6 . The cell differentiation promoter according to  claim 5 , wherein the hexuronic acid residue is a glucuronic acid residue or an iduronic acid residue. 
   
   
       7 . The cell differentiation promoter according to  claim 5  or  6 , wherein the glycosaminoglycan which has sulfate group and has the aforementioned characteristics (1) and (2) is 1 or 2 or more substances selected from a group consisting of a heparin, a substance which does not have the sulfate group on the 2-position hydroxyl group of the hexuronic acid residue of the heparin, a substance which does not have the sulfate group on the 6-position hydroxyl group of the glucosamine residue of the heparin and a substance which does not have the sulfate group on the 2-position amino group of the glucosamine residue of the heparin. 
   
   
       8 . The cell differentiation promoter according to  claim 5 , wherein the cell is a bone marrow-derived mesenchymal cell or an osteoblast. 
   
   
       9 . A cellular alkaline phosphatase activity reinforcing agent comprising, as an active ingredient, a glycosaminoglycan or a salt thereof which has a sulfate group and the characteristics of the following (1) and (2):
 (1) a basic structure is a disaccharide repeating structure consisting of a hexuronic acid residue and a glucosamine residue,   (2) one or less of the position among a 2-position hydroxyl group of the hexuronic acid residue, a 6-position hydroxyl group of the glucosamine residue and a 2-position amino group of the glucosamine residue in the basic structure of the aforementioned (1) does not have the sulfate group.   
   
   
       10 . The alkaline phosphatase activity reinforcing agent according to  claim 9 , wherein the hexuronic acid residue is a glucuronic acid residue or an iduronic acid residue. 
   
   
       11 . The alkaline phosphatase activity reinforcing agent according to  claim 9  or  10 , wherein the glycosaminoglycan which has sulfate group and the aforementioned characteristics (1) and (2) is 1 or 2 or more substances selected from a group consisting of a heparin, a substance which does not have the sulfate group on the 2-position hydroxyl group of the hexuronic acid residue of the heparin, a substance which does not have the sulfate group on the 6-position hydroxyl group of the glucosamine residue of the heparin and a substance which does not have the sulfate group on the 2-position amino group of the glucosamine residue of the heparin. 
   
   
       12 . The alkaline phosphatase activity reinforcing agent according to  claim 9 , wherein the cell is a bone marrow-derived mesenchymal cell or an osteoblast. 
   
   
       13 . Use of a glycosaminoglycan or a salt thereof which has a sulfate group and has characteristics of the following (1) and (2), for producing a hard tissue formation promoter:
 (1) a basic structure is a disaccharide repeating structure consisting of a hexuronic acid residue and a glucosamine residue,   (2) one or less of the position among a 2-position hydroxyl group of the hexuronic acid residue, a 6-position hydroxyl group of the glucosamine residue and a 2-position amino group of the glucosamine residue in the basic structure of the aforementioned (1) does not have the sulfate group.   
   
   
       14 . Use of a glycosaminoglycan or a salt thereof which has a sulfate group and has characteristics of the following (1) and (2), for producing a cell differentiation promoter:
 (1) a basic structure is a disaccharide repeating structure consisting of a hexuronic acid residue and a glucosamine residue,   (2) one or less of the position among a 2-position hydroxyl group of the hexuronic acid residue, a 6-position hydroxyl group of the glucosamine residue and a 2-position amino group of the glucosamine residue in the basic structure of the aforementioned (1) does not have the sulfate group.   
   
   
       15 . Use of a glycosaminoglycan or a salt thereof which has a sulfate group and has characteristics of the following (1) and (2), for producing a cellular alkaline phosphatase activity reinforcing agent:
 (1) a basic structure is a disaccharide repeating structure consisting of a hexuronic acid residue and a glucosamine residue,   (2) one or less of the position among a 2-position hydroxyl group of the hexuronic acid residue, a 6-position hydroxyl group of the glucosamine residue and a 2-position amino group of the glucosamine residue in the basic structure of the aforementioned (1) does not have the sulfate group.