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Metabolism. 1988 Oct;37(10):988-95.

Evidence that fluoride-stimulated 3[H]-thymidine incorporation in embryonic chick calvarial cell cultures is dependent on the presence of a bone cell mitogen, sensitive to changes in the phosphate concentration, and modulated by systemic skeletal effectors.

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Department of Medicine, Loma Linda University, CA.


In previous studies we have shown that clinically effective concentrations of fluoride (5 to 30 mumol/L) could also have direct effects in vitro on skeletal tissues to increase embryonic chick bone formation and bone cell proliferation (3[H]-thymidine incorporation into DNA). From these observations, we hypothesized that fluoride-stimulated bone formation might be mediated by a direct effect of fluoride to increase bone cell proliferation. The current studies were intended to investigate the mechanism of fluoride-stimulated 3[H]-thymidine incorporation, in chick calvarial cell cultures, by assessing mitogenic interactions between fluoride and inorganic phosphate, bone-derived growth factors, and systemic skeletal effectors. With respect to fluoride-phosphate interactions, the results of our studies indicate that the effect of fluoride was dependent on the phosphate concentration in the medium. Fluoride did not increase 3[H]-thymidine incorporation in BGJb medium containing 1 mmol/L (total) phosphate; but, in 1.6 mmol/L phosphate medium, fluoride caused a dose-dependent increase in 3[H]-thymidine incorporation, between 1 and 20 mumol/L (P less than .001). The action of fluoride was also dependent on the presence of a bone cell mitogen. Fluoride increased 3[H]-thymidine incorporation when added to calvarial cell cultures in the cell-conditioned medium, but had no effect in unconditioned (ie, fresh) medium. The action of fluoride could be restored by adding an exogenous growth factor (ie, concentrated cell-conditioned medium, bone-derived growth factors, or a systemic bone cell mitogen) to the unconditioned culture medium, P less than .05 for each effector.(ABSTRACT TRUNCATED AT 250 WORDS).

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