Fluoride's effects on the formation of teeth and bones, and the influence of genetics

Abstract

Fluorides are present in the environment. Excessive systemic exposure to fluorides can lead to disturbances of bone homeostasis (skeletal fluorosis) and enamel development (dental/enamel fluorosis). The severity of dental fluorosis is also dependent upon fluoride dose and the timing and duration of fluoride exposure. Fluoride's actions on bone cells predominate as anabolic effects both in vitro and in vivo. More recently, fluoride has been shown to induce osteoclastogenesis in mice. Fluorides appear to mediate their actions through the MAPK signaling pathway and can lead to changes in gene expression, cell stress, and cell death. Different strains of inbred mice demonstrate differential physiological responses to ingested fluoride. Genetic studies in mice are capable of identifying and characterizing fluoride-responsive genetic variations. Ultimately, this can lead to the identification of at-risk human populations who are susceptible to the unwanted or potentially adverse effects of fluoride action and to the elucidation of fundamental mechanisms by which fluoride affects biomineralization.

Figure 1.

Variation in dental fluorosis severity among inbred strains of mice. Mice at 5 to 6 wks of age were treated with fluoride (0 ppm or 50 ppm [F] ion) in the drinking water for 60 days. All strains developed dental fluorosis. Dental-fluorosis-susceptible strains are on the right, with those more resistant strains on the left side of the panel.

Figure 2.

Use of quantitative fluorescence to assess dental fluorosis. Panels A and C are clinical images of the mandibular incisors from A/J mice treated with control (0 ppm [F]), Panel A; and 50 ppm [F], Panel C) for 60 days. Panels B and D demonstrate the results of quantitative fluorescence (QF), where a Nikon epifluorescence microscope equipped with a Chroma Gold 11006v2 set cube (Spectra Services Inc., Ontario, NY, USA) (exciter D360/40x, dichroic 400DCLP, and emitter E515LPv2) was used to assess the severity of dental fluorosis. Increased fluorescence is associated with increased dental fluorosis severity.

Figure 3.

Schematic using inbred progenitor strains in a two-generation cross to produce a panel of F2 progeny. P1 and P2 are progenitor/parental strains that differ in a particular trait of response. The F1 progeny (1^st generation) are all genetically identical, having inherited half their genome from P1 and half their genome from P2. The F2 progeny (2^nd generation) are composed of genetically unique individuals.

Figure 4.

Dichotomy of fluoride responses between the high-bone-mass C3H/HeJ and low-bone-mass C57BL/6J inbred strains. The C57BL/6J strain favors the anabolic actions of fluoride, whereas the C3H/HeJ strain demonstrates enhanced osteoclastogenesis.