公开(公告)号：EP1119625B1

公开(公告)日：2005-06-29

申请号：EP99950250.3

申请日：1999-10-07

申请人： Medical College Of Georgia Research Institute, Inc.

发明人： ISALES, Carlos, M. ,  BOLLAG, Roni, J. ,  RASMUSSEN, Howard

IPC分类号： C12N15/16 ,  C07K14/605 ,  C07K16/26 ,  A61K38/26 ,  A01K67/027 ,  A61P19/10

CPC分类号： A01K67/0275 ,  A01K2217/05 ,  A01K2227/105 ,  A61K38/00 ,  C07K14/605

摘要： The examples demonstrate that GIP receptor mRNA and protein are present in normal bone and osteoblastic-like cell lines, and that high-affinity receptors for GIP can be demonstrated by 125 I GIP binding studies. When applied to osteoblast-like cells (SaOS2), GIP stimulated an increase in cellular cAMP content and in intracellular calcium, with both responses being dose dependent. Moreover, administration of GIP results in elevated expression of collagen type I mRNA as well as an increase in alkaline phosphatase activity. Both of these effects reflect anabolic actions of presumptive osteoblasts. These results provide the first evidence that GIP receptors are present in bone and osteoblastic-like cells and that GIP modulates the function of these cells. GIP has anabolic actions on remodeling bone, increasing vertebral bone density in a rat model of osteoporosis. GIP at 10nM inhibits PTH-induced bone resorption in a fetal long bone assay and stimulates the synthesis of type 1 collagen mRNA. Transgenic mice overexpressing GIP have increased bone density compared to same age controls. GIP or analogs thereof can therefore be used as a therapeutic to inhibit bone resorption and to maintain or increase bone density. GIP antagonists, compounds which block binding to the GIP receptor, can be used to decrease bone density.

公开(公告)号：EP1119625A1

公开(公告)日：2001-08-01

申请号：EP99950250.3

申请日：1999-10-07

申请人： Medical College Of Georgia Research Institute, Inc.

发明人： ISALES, Carlos, M. ,  BOLLAG, Roni, J. ,  RASMUSSEN, Howard

IPC分类号： C12N15/16 ,  C07K14/605 ,  C07K16/26 ,  A61K38/26 ,  A01K67/027

CPC分类号： A01K67/0275 ,  A01K2217/05 ,  A01K2227/105 ,  A61K38/00 ,  C07K14/605

摘要： The examples demonstrate that GIP receptor mRNA and protein are present in normal bone and osteoblastic-like cell lines, and that high-affinity receptors for GIP can be demonstrated by 125 I GIP binding studies. When applied to osteoblast-like cells (SaOS2), GIP stimulated an increase in cellular cAMP content and in intracellular calcium, with both responses being dose dependent. Moreover, administration of GIP results in elevated expression of collagen type I mRNA as well as an increase in alkaline phosphatase activity. Both of these effects reflect anabolic actions of presumptive osteoblasts. These results provide the first evidence that GIP receptors are present in bone and osteoblastic-like cells and that GIP modulates the function of these cells. GIP has anabolic actions on remodeling bone, increasing vertebral bone density in a rat model of osteoporosis. GIP at 10nM inhibits PTH-induced bone resorption in a fetal long bone assay and stimulates the synthesis of type 1 collagen mRNA. Transgenic mice overexpressing GIP have increased bone density compared to same age controls. GIP or analogs thereof can therefore be used as a therapeutic to inhibit bone resorption and to maintain or increase bone density. GIP antagonists, compounds which block binding to the GIP receptor, can be used to decrease bone density.