Background information: Fluoride is a well-known G-protein activator. Exposure of cultured cells to its derivatives results in actin cytoskeleton remodelling. Podosomes are actin-based structures endowed with adhesion and matrix-degradation functions. This study investigates actin cytoskeleton reorganization induced by fluoride in endothelial cells.
Results: Treatment of cultured endothelial cells with sodium fluoride (NaF) results in a rapid and potent stimulation of podosome formation. Furthermore, we show that Cdc42 (cell-division cycle 42), Rac1 and RhoA activities are stimulated in NaF-treated cells. However, podosome assembly is dependent on Cdc42 and Rac1, but not RhoA. Although the sole activation of Cdc42 is sufficient to induce individual podosomes, a balance between RhoGTPase activities regulates podosome formation in response to NaF, which in this case are often found in groups or rosettes. As in other models, podosome formation in endothelial cells exposed to NaF also involves Src. Finally, we demonstrate that NaF-induced podosomes are fully competent for matrix protein degradation.
Conclusions: Taken together, our findings establish NaF as a novel inducer of podosomes in endothelial cells in vitro.