Inhibition of bone resorption in vitro by compound 48/80.
The mechanisms that control cycles of bone formation and bone resorption are not well understood. In this report we provide evidence that compound 48/80 is a potent inhibitor of bone resorption in vitro. Resorption was assessed by the release of calcium-45 from pre-labelled newborn mouse calvaria that were treated with compound 48/80 and/or parathyroid hormone (PTH) in organ culture. Our results demonstrate that co-incubation of calvaria with PTH plus compound 48/80 (concentrations 1-10 mcg/ml) produces a marked reduction of calcium-45 release compared to PTH alone. Furthermore, pre-incubation of calvaria with compound 48/80, for as little as three hours, inhibits resorption by subsequent treatment with PTH alone. Measurement of lactate dehydrogenase (LDH) released into the culture medium indicated that treatment with compound 48/80, at the doses and time periods studied, was not cytotoxic. This novel effect of compound 48/80 may provide a useful tool for studying the cellular mechanisms involved in the bone resorption process.
D000818:Animals; D000831:Animals, Newborn; D001862:Bone Resorption / Q000187:drug effects*; D001842:Bone and Bones / Q000166:cytology; D002118:Calcium / Q000032:analysis; D002132:Calcium Radioisotopes; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D010281:Parathyroid Hormone / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
D002132:Calcium Radioisotopes; D010281:Parathyroid Hormone; D003189:p-Methoxy-N-methylphenethylamine; D002118:Calcium