Healthy Sprague-Dawley (SD) rats were randomly divided into four groups: the control group, the fluorosis group (F Group), the
fluoride + blocker group (F + Cycl group: rats were treated with
fluoride +
cyclopamine), and the
fluoride + blocker control group (F +
DMSO group). After 6 months of intervention, the urinary
fluoride content of rats in each group was detected. The primary osteoblasts of rats were selected for cell experiment, and the experiment was carried out after the cells were passaged from the second to the fourth generation.
RESULTS: The proliferation rate of primary rat osteoblasts presented time-affected and dose-affected relationships in a short time under treatment with a low dose of
sodium fluoride (NaF), but the proliferation of osteoblasts was inhibited by long-term and high-dose NaF exposure. In the F group, the
alkaline phosphatase (ALP) activity of osteoblasts increased gradually. The ALP activity was lower in the F + Cycl group than in the F group, and there was no significant difference between the F +
DMSO group and F group. With the increase in
fluoride exposure, the expression of Hh signal factors and osteogenic-related factor
proteins increased gradually. The expressions of Indian hedgehog (Ihh), smoothened (Smo),
Glioma-associated oncogene homolog (Gli) 2, and Runt-related
transcription factor 2 (Runx2)in the F + Cycl group increased with the dose of
fluoride but they were significantly inhibited compared with the F group. Compared with the control group, the content of urinary
fluoride in the F group was significantly higher (P < 0.05), but there was no significant change in urinary
fluoride content in the F + Cycl group and the F +
DMSO group. Compared with the control group, the serum bone
alkaline phosphatase (BALP) contents of rats in the other groups increased after 6 months' intake of
fluoride water (P < 0.05). After drug blocking, the serum BALP content in the F + Cycl group was lower than that in the F +
DMSO group (P < 0.05). The BALP content in the F +
DMSO group was similar to that in the F group: it did not decrease. The
mRNA expressions of Ihh, Smo, Gli2, and Runx2 in bone tissue of the F group were significantly higher than those in the control group (P < 0.05). After
cyclopamine blocking, the expressions decreased (P < 0.05), but the differences between the F +
DMSO group and F group were not statistically significant.
CONCLUSION: