title: Mechanism of aluminum-induced calcium efflux from cultured neonatal mouse calvariae.
abstract: Aluminum has been shown to increase unidirectional 45Ca efflux from prelabeled bones in vitro; whether aluminum affects net calcium efflux and, if so, by what mechanism has not been studied. To examine the effects of aluminum on net calcium flux from bone we cultured live and dead neonatal mouse calvariae with and without graded concentrations of aluminum (10(-8) to 10(-5) M). Aluminum induced a dose-dependent net calcium efflux from live bone after 24 h, but not 3 h, which was similar in magnitude to that produced by 10(-8) M parathyroid hormone. The normal calcium influx into dead bone was not altered by aluminum. Release of beta-glucuronidase, a lysosomal enzyme released by osteoclasts, increased after a 24-h incubation in aluminum-containing medium and was correlated with net calcium efflux. Calcitonin, an inhibitor of osteoclastic bone mineral dissolution, abolished the increase in beta-glucuronidase release and nullified the aluminum-induced net calcium efflux. Thus aluminum induces cell-mediated net calcium efflux from bone and increases beta-glucuronidase release. Calcitonin inhibits the increase in both calcium efflux and beta-glucuronidase release, suggesting that aluminum stimulates osteoclasts to release bone mineral.
authors.affiliation: Nephrology Program, Pritzker School of Medicine, University of Chicago, Illinois 60637.
authors.forename: S M
authors.initials: SM
authors.lastname: Sprague
authors.forename: D A
authors.initials: DA
authors.lastname: Bushinsky
mesh_terms: D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001696:Biomechanical Phenomena; D002116:Calcitonin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005966:Glucuronidase / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009924:Organ Culture Techniques; D012886:Skull / Q000166:cytology / Q000378:metabolism*
chemical_list: D002116:Calcitonin; D000535:Aluminum; D005966:Glucuronidase; D002118:Calcium