The Role of WDR72 in Amelogenesis

Abstract

Amelogenesis undergoes two stages; first a secretory stage followed by a maturation stage. During maturation, ameloblasts secrete kallikrein-4 (KLK4) enamel protease responsible for extra-cellular matrix degradation leading to ions deposition and enamel mineralization. Amelogenesis Imperfecta (AI) is a rare genetic disease affecting dental enamel formation. Patients with AI suffer from dental and esthetic problems. AI due to WDR72 mutations have weak and soft enamel phenotype similar to the phenotype seen with KLK4 mutations. The aims of this study were to investigate the stage at which WDR72 is expressed during amelogenesis and to investigate whether WDR72 has an effect on the extra-cellular location of KLK4. Immunohistochemistry with anti-WDR72 antibody was performed on WDR72 wild-type and knock-out rat molars to investigate the expression of WDR72 during secretory and maturation stages of amelogenesis. Mouse ameloblast-like cells were used to co-transfect WDR72 and KLK4 to examine the effects of WDR72 on KLK4 extra-cellular location. Our immunohistochemical staining data demonstrated that WDR72 was detected in the wild type ameloblasts during the maturation stage of amelogenesis. Our data also showed that the extracellular location of KLK4 was increased when WDR72 was co-transfected. In conclusion, our results demonstrated that WDR72 is highly expressed in ameloblasts at the maturation stage and that WDR72 is necessary for KLK4 extracellular location.