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Am J Physiol Renal Physiol 281: F1058-F1066, 2001. First published July 12, 2001; doi:10.1152/ajprenal.0355.2000
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Vol. 281, Issue 6, F1058-F1066, December 2001

Metabolic, but not respiratory, acidosis increases bone PGE2 levels and calcium release

David A. Bushinsky, Walter R. Parker, Kristen M. Alexander, and Nancy S. Krieger

Nephrology Unit, Department of Medicine, University of Rochester School of Medicine, Rochester, New York 14642

First published July 12, 2001; 10.1152/ajprenal.00355.2001.--- A decrease in blood pH may be due to either a reduction in bicarbonate concentration ([HCO<UP><SUB>3</SUB><SUP>−</SUP></UP>]; metabolic acidosis) or to an increase in PCO2 (respiratory acidosis). In mammals, metabolic, but not respiratory, acidosis increases urine calcium excretion without altering intestinal calcium absorption, indicating that the additional urinary calcium is derived from bone. In cultured bone, chronic metabolic, but not respiratory, acidosis increases net calcium efflux (JCa), decreases osteoblastic collagen synthesis, and increases osteoclastic bone resorption. Metabolic acidosis increases bone PGE2 production, which is correlated with JCa, and inhibition of PGE2 production inhibits this acid-induced JCa. Given the marked differences in the osseous response to metabolic and respiratory acidosis, we hypothesized that incubation of neonatal mouse calvariae in medium simulating respiratory acidosis would not increase medium PGE2 levels, as observed during metabolic acidosis. To test this hypothesis, we determined medium PGE2 levels and JCa from calvariae incubated at pH ~7.1 to model either metabolic (Met; [HCO<UP><SUB>3</SUB><SUP>−</SUP></UP>] ~11 mM) or respiratory (Resp; PCO2 ~83 Torr) acidosis, or at pH ~7.5 as a control (Ntl). We found that after 24-48 and 48-51 h in culture, periods when cell-mediated JCa predominates, medium PGE2 levels and JCa were increased with Met, but not Resp, compared with Ntl, and there was a direct correlation between medium PGE2 levels and JCa. Thus metabolic, but not respiratory, acidosis induces the release of bone PGE2, which mediates JCa from bone.

calvariae; osteoblasts; protons; pH


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