Chronic metabolic acidosis reversibly inhibits extracellular matrix
gene expression in mouse osteoblasts.
Frick, Kevin K., and David A. Bushinsky.
Nephrology Unit, Department of Medicine, University of Rochester
School of Medicine, Rochester, NY 14642
APStracts 5:0141F, 1998.
Chronic metabolic acidosis induces net calcium efflux from bone
mineral through an increase in osteoclastic resorption and a decrease
in osteoblastic matrix deposition and mineralization. To determine
the effects of chronic metabolic acidosis on the expression of genes
necessary for mineralization, we grew primary bone cells, which are
principally osteoblasts, to confluence in neutral pH (7.5) medium and
then switched the cells either to a neutral pH or to an acidic pH
(7.1) differentiation medium. Cells were harvested for RNA at 4-7 d
intervals for up to 44 d. By 36 d, there was extensive bone nodule
formation and mineralization in cells cultured in neutral medium;
however, there was a substantial decrease in nodule formation and
mineralization in cells cultured in acidic medium. There was a marked
increase in matrix Gla protein RNA and an increase in osteopontin RNA
in neutral cultures; however, acidic medium almost completely
suppressed these increases. In contrast, RNA levels for osteonectin
and transforming growth factor [beta]1 were not altered by chronic
acidosis. Additional cells were incubated in acid differentiation
medium for 1, 2 or 3 weeks and then transferred to neutral medium; in
each case there was recovery of matrix Gla protein RNA and
osteopontin RNA expression. Still other cells were incubated in
neutral differentiation medium for 1, 2 or 3 weeks and then
transferred to acid medium; in each case there was inhibition of
matrix Gla protein RNA and osteopontin RNA expression. Thus metabolic
acidosis appears to specifically inhibit RNA accumulation of certain
genes whose products may be essential for formation of mature bone
matrix.
Received 20 March 1998; accepted in final form 16 August 1998.
APS Manuscript Number F68-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 21 September 1998