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.