On the role of cyclic AMP as a mediator of bone resorption: gamma-interferon completely inhibits cholera toxin- and forskolin-induced but only partially inhibits parathyroid hormone-stimulated 45Ca release from mouse calvarial bones.
The effects of gamma-interferon (gamma-IFN) on bone resorption and cyclic AMP formation stimulated by parathyroid hormone (PTH), forskolin, and cholera toxin have been studied in cultured neonatal mouse calvarial bones. Bone resorption was assessed by the release of 45Ca from prelabeled mouse calvarial bone fragments. Cyclic AMP formation was quantified by analyzing the amount of the nucleotide in calvarial bone tissue. gamma-IFN completely blocked the 45Ca release response to forskolin and cholera toxin in 96 h cultures. In contrast, the 45Ca release response to PTH was only partially inhibited, an effect that was seen over a wide range of PTH concentrations. The inhibitory effect of gamma-IFN was dose dependent, with a threshold for action at 10 U/ml. Forskolin-stimulated 45Ca release could only be inhibited when gamma-IFN was added simultaneously with forskolin; gamma-IFN added to bones prestimulated with forskolin had no effect. The inhibitory effect of gamma-IFN on PTH-stimulated 45Ca release was seen first after a time lag of 48 h. In contrast calcitonin caused an inhibition after only 3 h. PTH and cholera toxin stimulation of radioactive calcium release was also inhibited by gamma-IFN in bones treated with indomethacin. gamma-IFN inhibited forskolin-induced 45Ca release in bones treated with the mitotic inhibitor hydroxyurea. No effect of gamma-IFN on cyclic AMP formation induced by PTH, cholera toxin, or forskolin could be seen. These data show that gamma-IFN inhibits forskolin- and cholera toxin-induced bone resorption by a mechanism unrelated to prostaglandin production or mitotic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Lerner
U H
UH
Department of Oral Pathology, University of Umeå, Sweden.
Ransjö
M
M
Ljunggren
O
O
Klaushofer
K
K
Hoffmann
O
O
Peterlik
M
M
D000818:Animals; D001862:Bone Resorption / Q000503:physiopathology*; D001842:Bone and Bones / Q000378:metabolism*; D002116:Calcitonin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002772:Cholera Toxin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D046508:Culture Techniques; D000242:Cyclic AMP / Q000378:metabolism*; D006918:Hydroxyurea / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010294:Parietal Bone
D010281:Parathyroid Hormone; D005576:Colforsin; D007371:Interferon-gamma; D002116:Calcitonin; D002772:Cholera Toxin; D000242:Cyclic AMP; D002118:Calcium; D006918:Hydroxyurea; D007213:Indomethacin