Prostaglandins regulate acid-induced cell-mediated bone resorption.
Metabolic acidosis induces bone calcium efflux initially by physicochemical dissolution and subsequently by cell-mediated mechanisms involving inhibition of osteoblasts and stimulation of osteoclasts. In rat kidney, acidosis increases endogenous prostaglandin synthesis, and in bone, prostaglandins are important mediators of resorption. To test the hypothesis that acid-induced bone resorption is mediated by prostaglandins, we cultured neonatal mouse calvariae in neutral or physiologically acidic medium with or without 0.56 microM indomethacin to inhibit prostaglandin synthesis. We measured net calcium efflux and medium PGE(2) levels. Compared with neutral pH medium, acid medium led to an increase in net calcium flux and PGE(2) levels after both 48 h and 51 h, a time at which acid-induced net calcium flux is predominantly cell mediated. Indomethacin inhibited the acid-induced increase in both net calcium flux and PGE(2). Net calcium flux was correlated directly with medium PGE(2) (r = 0.879, n = 29, P < 0.001). Exogenous PGE(2), at a level similar to that found after acid incubation, induced net calcium flux in bones cultured in neutral medium. Acid medium also stimulated an increase in PGE(2) levels in isolated bone cells (principally osteoblasts), which was again inhibited by indomethacin. Thus acid-induced stimulation of cell-mediated bone resorption appears to be mediated by endogenous osteoblastic PGE(2) synthesis.
Krieger
N S
NS
Department of Medicine, Nephrology Unit, University of Rochester School of Medicine, Rochester, New York 14642, USA. Nancy_Krieger@urmc.rochester.edu
Parker
W R
WR
Alexander
K M
KM
Bushinsky
D A
DA
D000138:Acidosis / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D001639:Bicarbonates / Q000378:metabolism; D001862:Bone Resorption / Q000378:metabolism* / Q000473:pathology*; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D006863:Hydrogen-Ion Concentration; D051379:Mice; D009924:Organ Culture Techniques; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D012886:Skull / Q000166:cytology / Q000378:metabolism
D001639:Bicarbonates; D011453:Prostaglandins; D002245:Carbon Dioxide; D015232:Dinoprostone; D002118:Calcium