HYPOTHESES ABOUT THE MOLECULAR MECHANISM UNDERLYING THE MITOGENIC ACTIVITY OF FLUORIDE IN BONE CELLS

Abstract

Fluoride is a potent stimulator of bone formation because it increases differentiation and proliferation of osteoblasts. This effect would be the consequence of two putative mechanism: 1- fluoride inhibits a tyrosin phosphatase of osteoblasts, which dephosphorylates cytosolic domains of tyrosin kinase receptors. As a consequence the half-life of phosphorylated kinases increases, enhancing the effect of some growth factors. On the other hand, fluoride would stimulate G proteins which stimulates signaling pathways that involved ERK kinases. The result of these effects is an increase in differentiation of osteoblasts in vitro and in vivo, in the expression of alkaline phosphatase in the membrane of precursors of osteoblasts and in the production of osteocalcin.