title: High-fluoride acitivates the FasL signalling pathway and leads to damage of ameloblast ultrastructure.
abstract: OBJECTIVE
  High 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.
  
  
  METHODS
  Primary ameloblasts were isolated from the molar tooth germ of 4-day-old SD rats. The ameloblasts were incubated with 3.2mM NaF or nothing. After incubation for different time arranging from 12h to 72h, ELISA was used to detected the secretion levels of FasL in the medium. Then at 48h 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.
  
  
  RESULTS
  The secretion of FasL was notably increased by 3.2mM NaF treatment, and the increase reached to the peak after incubation for 48h. 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.
  
  
  CONCLUSIONS
  High-fluoride leads to damage of the ameloblast ultrastructure through paritially acitivating the FasL signalling pathway.
authors.affiliation: Department of Stomatology, Xi'an Medical University, Xi'an, China. Electronic address: scarlettwn15@163.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Stomatology, Xi'an Medical University, Xi'an, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Stomatology, Xi'an Medical University, Xi'an, China.
authors.forename: Danyang
authors.initials: D
authors.lastname: Wang
mesh_terms: D000565:Ameloblasts / Q000187:drug effects* / Q000648:ultrastructure*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008854:Microscopy, Electron; D008963:Molar; D018384:Oxidative Stress; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D012969:Sodium Fluoride / Q000494:pharmacology*; D014083:Tooth Germ / Q000187:drug effects
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D012969:Sodium Fluoride
keywords: Ameloblast; FasL; High-fluoride; Ultrastructure