Evidence for regulation of amelogenin gene expression by 1,25-dihydroxyvitamin D-3 in vivo

The unique hereditary enamel defect clearly related to the disturbance of o ne enarmel matrix protein is X-linked amelogenesis imperfecta (Al), in whic h several mutations of amelogenin gene have been identified. The clinical p henotype of many of these subjects shows similarities with enamel defects r elated to rickets. Therefore, we hypothesized that rachitic dental dysplasi a is related to disturbances in the amelogenin pathway. In order to test th is hypothesis, combined qualitative and quantitative studies in experimenta l vitamin D-deficient (-D) rat model systems were performed; First, Western blot analysis of microdissected enamel matrix (secretion and maturation st ages) showed no clear evidence of dysregulation of amelogenin protein proce ssing in -D rats as compared with the controls. Second, the ultrastructural investigation permitted identification of the internal tissular defect of rachitic enamel, the irregular absence of intraprismatic enamel observed in -D animals, suggesting a possible link between prism morphogenesis-and vit amin D. In addition, the steady-state levels of amelogenin mRNAs measured i n microdissected dental cells was decreased in -D rats and up-regulated by an unique injection of 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3). The pres ent study shows evidences that amelogenin expression is regulated by vitami n D. This is the first study of an hormonal regulation of tooth-specific ge nes.(C) 1999 Wiley-Liss, Inc.