High-fluoride acitivates the FasL signalling pathway and leads to damage of ameloblast ultrastructure

•FasL secretion was increased by high fluoride incubation in rat ameloblasts;.•High fluoride caused a series of cell organelle destruction in the ameloblasts;.•High fluoride increased expression of apoptotic genes and oxidative stress;.•The FasL inhibitor partially mitigated the ultrastructure damage.

ObjectiveHigh fluoride can induce stress-mediated apoptosis and degradation of ameloblasts. Fas ligand (FasL) has been regarded as a key regulator in intracellular responses for stress-induced apoptosis in reproductive or cancerous cell lineages. The objective of this study is to explore the role of FasL in the regulation of ameloblast ultrastructure damage.DesignPrimary ameloblasts were isolated from the molar tooth germ of 4-day-old SD rats. The ameloblasts were incubated with 3.2 mM NaF or nothing. After incubation for different time arranging from 12 h to 72 h, ELISA was used to detected the secretion levels of FasL in the medium. Then at 48 h post treatment, the ameloblast ultrastructure was detected with Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM), and expression of apoptotic proteins and peroxidative enzymes/products were examined. Finally, a specific FasL inhibitor was applied to co-treat the ameloblasts with NaF, and the ameloblast ultrastructure was detected with TEM and SEM.ResultsThe secretion of FasL was notably increased by 3.2 mM NaF treatment, and the increase reached to the peak after incubation for 48 h. High fluoride incubation damaged the ameloblast untrastructure manifesting a series of intracelluar stress responsing cell organelle destruction, and a marked increase in expression of apoptotic genes and oxidative stress. The FasL inhibitor treatment partially mitigated the untrastructure damage caused by high dose NaF.ConlusionHigh-fluoride leads to damage of the ameloblast ultrastructure through paritially acitivating the FasL signalling pathway.