Effects of Fluoride on the Osteoblastic Activities and Osteoclast Generation In Vitro

Abstract

In an effort to assess the effects of F on overall bone metabolism, cultures of osteoblastic cells isolated from fetal rat calvaria for bone formation in vitro, and of mouse bone marrow cells to generate osteoclast-like cells were conducted. Considerable number of mineralized nodules was developed in osteoblastic cell cultures maintained in the presence of ascorbic acid and β-glycerophosphate up to 21 days. The number of mineralixed nodules was not increased significantly by continuous treatment of cultures with 10 μM NaF, a clinically effective osteogenic concentration. When cultures were treated with pulses of 48 hr-duration before apparent mineralization was occurring, 1.8-fold increase in their number was detected. Addition of 10 μN NaF with onset of mineralization exhibites an inhibitory tendency on the formation of mineralixed nodules. In the subsequent study, NaF stimulated [^3H]thymidine incorporation in osteoblastic cells both under serum-supplemented and serum-free conditions. Alkaline phosphatase activity of osteoblastic cells was not changed by NaF over the concentration ranges examined. Rather a dose-dependent inhibition appeared with extension of treatment duration. Osteoclast-like cell generation in cultures of mouse bone marrow cells induced by PGE_2 and PGE_2 plus IL-6 was significantly inhibited by NaF at the relatively higher concentrations. but not at 10 μM. And IL-6 production in osteoblastic cells was also decreased by NoF only at higher concentrations. These results taken together suggest that F enhances bone formation and the stimulatory effect of F on the proliferation of osteoblastic cells is probably most relevant to its mechanism underlying augmented bone formation.