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Effect of fluoride on osteoclast formation at various levels of receptor activator of nuclear factor Kappa-B ligand (RANKL).Abstract
Receptor activator of nuclear factor kappa-B ligand (RANKL) acting on osteoblasts is an essential cytokine for osteoclast formation. Recent studies have shown that fluoride (F) can stimulate RANKL expression of osteoblasts. However, the effect of F under various levels of RANKL on osteoclast formation is not clear. In this study, stem cell technology was used to observe the effect of F on osteoclast formation at different levels of treatment with RANKL. Our results show that F significantly inhibits the formation of osteoclasts treated with 50 ng/mL RANKL. The number of osteoclasts in the 0.5 mg/L F group fell to about 60% of the control group with no further significant change at the higher fluoride concentrations used (2 and 8 mg/L). On the other hand, F had no effect on the formation of osteoclasts treated with 100 ng/mL RANKL. In fact, the number of osteoclasts formed at 100 ng/mL RANKL was significantly higher than at the 50 ng/mL RANKL level. However, F significantly decreased the activity of osteoclast bone resorption even at a low level of 0.5 mg/L F, and the higher the F concentration was, the lower the activity of bone resorption became. Therefore we conclude that the main effect of F on osteoclasts was the inhibition of their capacity for bone resorption, thus resulting in osteosclerosis as the major clinical manifestation in patients with skeletal fluorosis.