Methods of screening for apoptosis-controlling agents for...

A - Human Necessities – 61 – K

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Details

A61K 38/29 (2006.01) A61K 31/00 (2006.01) A61K 31/05 (2006.01) A61K 31/11 (2006.01) A61K 31/565 (2006.01) A61K 31/567 (2006.01) A61K 45/06 (2006.01) A61K 49/00 (2006.01) A61P 19/10 (2006.01) C12Q 1/00 (2006.01) C12Q 1/06 (2006.01) G01N 33/50 (2006.01) G01N 33/74 (2006.01)

Patent

CA 2346695

The present invention demonstrates that human parathyroid hormone 1-34 [hPTH(1- 34)] exerts anti-apoptotic effects on osteoblasts when administered in an intermittent fashion to mice in vivo. The present invention further demonstrates that bovine PTH(1-34) [bPTH(1-34)] prevents glucocorticoid- induced apoptosis of osteoblastic and osteocytic cells in vitro. Therefore, the present invention demonstrates that the previously established anabolic effects of PTH on the skeleton are mediated by its ability to postpone osteoblast apoptosis, as opposed to a stimulatory effect on osteoblastogenesis. The present invention provides methods of screening agents for anti-apoptotic effects on osteoblasts, wherein such agents stimulate and/or restore bone in osteopenic individuals, or prevent bone loss caused by agents such as glucocorticoids.

La présente invention vise à démontrer que l'hormone parathyroïdienne humaine 1-34 [hPTH(1-34)] exerce des effets anti-apoptotiques sur les ostéoblastes lorsqu'on l'administre in vivo de manière intermittente à des souris. La présente invention vise également à démontrer que la PTH(1-34) [bPTH(1-34)] empêche l'apoptose in vivo, induite par les glucocorticoïdes, des cellules ostéoblastiques et ostéocytiques. Cette invention tend par conséquent à démontrer que les effets anabolisants précédemment établis de la PTH sur le squelette résultent de sa capacité à retarder l'apoptose des ostéoblastes, qui s'oppose à un effet stimulant sur l'ostéoblastogenèse. La présente invention se rapporte à des procédés de détection d'agents possédant des pouvoirs anti-apoptotiques sur les ostéoblastes, lesdits agents stimulant et/ou reconstituant l'os chez des sujets ostéopéniques ou empêchant les pertes osseuses au moyen d'agents tels que les glucocorticoïdes.

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