In vivo and in vitro evidence for the involvement of cysteine proteinases in bone resorption.
The excretion of cathepsin B, a lysosomal cysteine proteinase, by parathyroid hormone-stimulated embryonic mouse calvaria in culture, correlates closely with the extent of bone resorption evaluated by the loss of hydroxyproline and calcium and by the extension of resorption lacunae. E-64, a specific inhibitor of cysteine proteinases, inhibits reversibly the resorption of cultured bones without affecting the hormone-induced secretion of lysosomal hydrolases. Given in vivo to rats, the proteinase inhibitors, E-64 and leupeptin, both induce a concomitant fall in the serum calcium level and in the urinary excretion of hydroxyproline. These results provide evidence that cysteine proteinases, possibly lysosomal cathepsins, are necessary for bone resorption.
D000818:Animals; D001862:Bone Resorption; D001842:Bone and Bones / Q000196:embryology / Q000201:enzymology; D002118:Calcium / Q000097:blood; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D004622:Embryo, Mammalian; D010450:Endopeptidases / Q000378:metabolism*; D005260:Female; D006026:Glycoside Hydrolases / Q000378:metabolism; D006909:Hydroxyproline / Q000032:analysis; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D011480:Protease Inhibitors; D006026:Glycoside Hydrolases; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D006909:Hydroxyproline; D002118:Calcium