title: 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.
abstract: 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)
authors.affiliation: Department of Medicine, Loma Linda University, CA.
authors.forename: J R
authors.initials: JR
authors.lastname: Farley
authors.forename: N
authors.initials: N
authors.lastname: Tarbaux
authors.forename: S
authors.initials: S
authors.lastname: Hall
authors.forename: D J
authors.initials: DJ
authors.lastname: Baylink
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D002478:Cells, Cultured; D002642:Chick Embryo; D005459:Fluorides / Q000494:pharmacology*; D006133:Growth Substances / Q000378:metabolism* / Q000502:physiology; D010710:Phosphates / Q000378:metabolism*; D012886:Skull / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D013268:Stimulation, Chemical; D013936:Thymidine / Q000378:metabolism*
chemical_list: D006133:Growth Substances; D010710:Phosphates; D005459:Fluorides; D013936:Thymidine