Fluoride-Treated Bio-Resorbable Synthetic Hydroxyapatite Promotes Proliferation and Differentiation of Human Osteoblastic MG-63 Cells

When resorbable hydroxyapatite (HA) granules, which are used as a bone supplement material, were treated in neutral 4% sodium fluoride (NaF) solution, formation of a reactant resembling calcium fluoride was observed on the surface of the granules. Immediate and slow release of fluoride from fluoridated HA (HA+F) granules was observed after immersion in culture fluid, and the concentration increased over time to 1.25 ± 0.05 ppm F at 0.5 hours, 1.57 ± 0.12 ppm F at 24 hours, and 1.73 ± 0.15 ppm F at 48 hours. On invasion assay, migration of human osteoblast-like MG-63 cells exposed to the released fluoride was confirmed in comparison to the cells incubated with a nonfluoridated control sample (P < .01). In addition, fluoride added to the medium increased MG-63 cell proliferation in a manner dependent on fluoride concentrations up to 2.0 ppm (P < .05). At 5.0 ppm, however, fluoride significantly inhibited cell proliferation (P < .005). Activity of the osteogenic differentiation marker, alkaline phosphatase (ALP), also increased with fluoride after exposure for 1 week, increasing significantly at 1.0 ppm (P < .05). The promotion of MG-63 cell migration and proliferation, as well as increased ALP activity, suggested that fluoride released from the surface of resorbable HA granules, which were fluoridated by prior treatment with neutral 4% NaF solution, can provide a superb method to supply fluoride and promote osteogenic cell differentiation.