Acute metabolic acidosis inhibits the induction of osteoblastic
egr-1 and type 1 collagen.
Frick, Kevin K., Li Jiang, and David A. Bushinsky.
Nephrology Unit, Department of Medicine, University of Rochester,
Rochester, NY 14642
APStracts 3:0413C, 1996.
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 of 7.4, RNA for Egr-1 was stimulated
approximately 30-50 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 I collagen was stimulated approximately 3-5
fold, 40 min after medium change. Again the stimulation was inhibited
by acidosis and increased by alkalosis. Cycloheximide abolished the
pH dependency of expression. These results suggest that small changes
in external pH have a significant effect on the expression of certain
genes important for osteoblastic function.
Received 17 April 1996; accepted in final form 16 December 1996.
APS Manuscript Number C211-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996