A new synthetic inhibitor of mammalian tissue collagenase inhibits bone resorption in culture.
A specific and potent synthetic inhibitor of mammalian tissue collagenase and related metallo-proteinases inhibits the collagen matrix resorption induced by parathyroid hormone (PTH) in cultured embryonic mouse calvaria. The inhibition is reversible, dose-dependent and virtually complete at 50 microM inhibitor concentration whereas that due to a less potent stereoisomer is much weaker. The PTH-enhanced secretion of calvarial lysosomal enzymes and the small spontaneous leakage of lactate dehydrogenase are not affected by the inhibitor. These results suggest that collagenase plays a critical role in bone resorption. Its role is discussed in relation to that of cysteine-proteinases that have also been implicated in this process.
D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D046508:Culture Techniques; D004622:Embryo, Mammalian; D006909:Hydroxyproline / Q000378:metabolism; D051379:Mice; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology*; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013237:Stereoisomerism
D009842:Oligopeptides; D010281:Parathyroid Hormone; C047473:N-(3-N-(benzyloxycarbonyl)amino-1-carboxypropyl)leucyl-O-methyltyrosine N-methylamide; D003012:Microbial Collagenase; D006909:Hydroxyproline; D002118:Calcium