Beta 2-microglobulin induces calcium efflux from cultured neonatal mouse calvariae.
beta 2-Microglobulin (beta 2M) polymerizes to form amyloid fibrils that deposit and cause destructive bone lesions in patients on chronic dialytic therapy. beta 2 M is mitogenic to osteoblasts; however, its effect on bone mineralization is unknown. To determine whether beta 2M causes bone demineralization, neonatal mouse calvariae were incubated with and without beta 2M, and net calcium flux was calculated. Following a 48-h but not 3- or 24-h incubation, beta 2M (10(-8)-10(-6) M) induced a net calcium efflux. The efflux was similar to that observed with 10(-10) M parathyroid hormone (PTH) but less than that observed with 10(-8 M PTH. Devitalizing the calvariae resulted in a net calcium influx that was unaffected by the addition of beta 2M, indicating a cell-mediated phenomenon. The release of beta-glucuronidase, an osteoclast enzyme, increased after a 48-h but not a 24-h incubation with beta 2M. Calcitonin, an osteoclast inhibitor, blocked the beta 2M-induced calcium efflux and beta-glucuronidase release, suggesting osteoclast involvement. Thus beta 2M induces a dose- and time-dependent, cell-mediated calcium efflux from neonatal mouse calvariae that involves osteoclast stimulation.
Moe
S M
SM
Nephrology Program, Pritzker School of Medicine, University of Chicago, Illinois 60637.
Sprague
S M
SM
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002116:Calcitonin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005966:Glucuronidase / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D008815:Mice, Inbred Strains; D009924:Organ Culture Techniques; D010010:Osteoclasts / Q000378:metabolism; D012886:Skull / Q000166:cytology / Q000378:metabolism*; D001613:beta 2-Microglobulin / Q000494:pharmacology*
D001613:beta 2-Microglobulin; D002116:Calcitonin; D000135:Acid Phosphatase; D005966:Glucuronidase; D002118:Calcium