Acute metabolic acidosis inhibits the induction of osteoblastic egr-1 and type 1 collagen

The American Journal of Physiology
Kevin K FrickD A Bushinsky

Abstract

Metabolic acidosis induces net calcium efflux from bone through a decrease in osteoblastic formation and an increase in osteoclastic resorption. We tested the hypothesis that changes in external pH would alter the expression of genes critical to the function of mouse calvarial bone cells, predominantly osteoblasts. Cells were cultured in physiologically neutral pH medium until confluent and then stimulated with fresh medium at either neutral or acidic pH. Among a group of immediate early response genes, including egr-1, junB, c-jun, junD, and c-fos, only egr-1 stimulation was modulated by changes in medium pH. At pH 7.4, RNA for egr-1 was stimulated approximately 10- to 30-fold, 40 min after medium change. A progressive decrease in pH to 6.8 led to a parallel reduction in egr-1 stimulation, and an increase in pH to 7.6 led to an increase in egr-1 stimulation. The protein synthesis inhibitor cycloheximide led to a superinduction of egr-1 with preservation of the pH dependency of expression. Osteoblasts synthesize collagen, which is subsequently mineralized. RNA for type 1 collagen was stimulated approximately three- to fivefold, 40 min after medium change. Again the stimulation was inhibited by acidosis and increased by alkalosi...Continue Reading

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Citations

Sep 14, 1999·The American Journal of Physiology·A Santhanagopal, S J Dixon
Nov 30, 2000·American Journal of Physiology. Renal Physiology·N S KriegerD A Bushinsky
Dec 21, 2000·American Journal of Physiology. Cell Physiology·J A SpectorM T Longaker
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Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
Kevin K Frick, D A Bushinsky
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