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Nephrology Unit, Department of Medicine, University of Rochester School of Medicine, Rochester, New York 14642
Clinically, a
decrease in blood pH may be due to either a reduction in bicarbonate
concentration ([HCO
3], metabolic acidosis) or an increase in
PCO2 (respiratory acidosis). In
mammals, metabolic acidosis induces a far greater increase in urine
calcium excretion than respiratory acidosis. In cultured bone,
metabolic acidosis induces a marked increase in calcium efflux and a
decrease in osteoblastic collagen synthesis, whereas isohydric
respiratory acidosis has little effect on either parameter. We have
shown that metabolic acidosis prevents the normal developmental
increase in the expression of RNA for matrix Gla protein
and osteopontin in chronic cultures of primary murine calvarial bone
cells (predominantly osteoblasts) but does not alter expression of
osteonectin. To compare the effects of isohydric metabolic and
respiratory acidosis on expression of these genes, bone cell cultures
were incubated in medium at pH ~7.2 to model metabolic
([HCO3], ~13 mM) or
respiratory (PCO2, ~80 mmHg)
acidosis or at pH ~7.4 as a control. Cells were sampled at
weeks 4,
5, and
6 to assess specific RNA content. At
all time periods studied, both metabolic and respiratory acidosis
inhibited the expression of RNA for matrix Gla protein and osteopontin
to a similar extent, whereas there was no change in osteonectin
expression. In contrast to the significant difference in the effects of
metabolic and respiratory acidosis on bone calcium efflux and
osteoblastic collagen synthesis, these two forms of acidosis have a
similar effect on osteoblastic RNA expression of both matrix Gla
protein and osteopontin. Thus, although several aspects of bone cell
function are dependent on the type of acidosis, expression of these two matrix genes appears to be regulated by extracellular pH, independently of the type of acidosis.
bone; matrix Gla protein; osteonectin; osteopontin
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