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The Effect of Sodium Fluoride on the Physiological Role of Osteoblastic Cell

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Abstract


The clinical use of fluoride with a well known osteogenic action in osteoporo>tic patients
is rational, because this condition is characterized by impaired bone formation. However, its anabolic effect has not been demonstrated well in vitro. The purpose of this study was to investigate the effects of sodium fluoride on the physiological role of osteoblastic cell. Osteoblastic cells were isolated from fetal rat calvaria.
The results were as follows
1. Considerable number of mineralized nodules were shown in osteoblastic cell cultures, which had been maintained in the presence of ascorbic acid and 6 -glycerophosphate up to 21 days. The number of mineralized nodules was not increased significantly by continuous treatment of cultures with 10 P M sodium fluoride. When cultures were treated with pulses of 48 hr duration before apparent mineralization was occurring, 2-fold increased in their number was detected.
2. Alkaline phosphatase activity of osteoblastic cells was inhibited by- sodium fluoride in dose-dependent manner.
3. Sodium fluoride stimulated proliferation in osteoblastic cells. The effect of sodium fluoride on the cell proliferation was measured by the incorporation of [3H]-thymidine into DNA. As a result, sodium fluoride at 1--100 u M increased the (3H]-thymidine incorporation into DNA in a dose dependent manner. These results taken together suggested that sodium fluoride enhanced bone formation and that the stimulatory effect of fluoride on the proliferation of osteoblastic cells was probably most relevant to its mechanism underlying augmented bone formation. Sodium fluoride, which was probably the molecule responsible for the mitogenic effect of fluoride in MC3T3E1 osteoblast-like cells, modulated a tyrosine phosphorylation pathway linked to mitogen-activated protein kinase(MAPK).
4. The signaling mechanism activated by sodium fluoride dose-dependently enhanced the tyrosine phosphorylation of the adaptor molecule Shc`yi¢¥ and their association with Grb2, one of earlier events in a MAP kinase activation pathway cascade used by a significant subset of G protein-coupled receptors.

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