Dental follilce cells and cementiblasts induce apoptosis of ameloblast-lineage and Hertwig's epithelial root sheath/epithelial rests of Malassez cells through the Fas-Fas ligand pathway

Abstract

Hertwig s epithelial root sheath (HERS), epithelial rests of Malassez (ERM) cells, andreduced ameloblasts undergo apoptosis during tooth development. This study examinedthe effects of dental follicle cells and cementoblasts on the apoptosis of ameloblast-lineage and HERS/ERM cells derived from the enamel organ. We alsoelucidated the induction pathways and identified the apoptotic pathway involved inthis process. Here, we showed terminal deoxynucleotidyl transferase-mediated biotin.dUTP nick-end labeling (TUNEL)-positive HERS cells and reduced ameloblasts neardental follicle cells during tooth development. Co-culturing ameloblast-lineage cell line(ALC) ameloblasts and HERS/ERM cells with either dental follicle cells or OCCM-30cementoblasts markedly enhanced the apoptosis of ameloblasts and HERS/ERM cellscompared with cells cultured alone. However, dental follicle cells and cementoblastsdid not modulate the apoptotic responses of co-cultured non-odontogenic MCF10Aor KB cells. When ameloblasts + HERS and cementoblasts + dental follicle cellswere co-cultured, the expression of Fas ligand (FasL) increased in cementoblasts+ dental follicle cells, while the expression of Fas increased in ameloblasts+ HERS. Interestingly, recombinant FasL induced ameloblast apoptosis whilethe cementoblast-induced ameloblast apoptosis was suppressed by the Fas/FasLantagonist Kp7-6. These results suggest that during tooth development, dental folliclecells and cementoblasts induce apoptosis of ameloblast-lineage and HERS/ERM cellsthrough the Fas.FasL pathway, but do not induce the apoptosis of non-odontogenicepithelial cells.