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 one enamel matrix protein is X-linked amelogenesis imperfecta (AI), in which several mutations of amelogenin gene have been identified. The clinical phenotype of many of these subjects shows similarities with enamel defects related to rickets. Therefore, we hypothesized that rachitic dental dysplasia is related to disturbances in the amelogenin pathway. In order to test this hypothesis, combined qualitative and quantitative studies in experimental vitamin D-deficient (-D) rat model systems were performed. First, Western blot analysis of microdissected enamel matrix (secretion and maturation stages) showed no clear evidence of dysregulation of amelogenin protein processing 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 vitamin D. In addition, the steady-state levels of amelogenin mRNAs measured in 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 present study shows evidences that amelogenin expression is regulated by vitamin D. This is the first study of an hormonal regulation of tooth-specific genes.
Papagerakis
P
P
Laboratoire Biologie-Odontologie, Facult¿e de Chirurgie Dentaire, Universit¿e Paris VII, Paris 75006, France. papagera@infobiogen.fr
Hotton
D
D
Lezot
F
F
Brookes
S
S
Bonass
W
W
Robinson
C
C
Forest
N
N
Berdal
A
A
D000566:Amelogenesis / Q000187:drug effects / Q000235:genetics; D000567:Amelogenesis Imperfecta / Q000235:genetics; D053523:Amelogenin; D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology*; D003743:Dental Enamel / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D003746:Dental Enamel Proteins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008854:Microscopy, Electron; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014808:Vitamin D Deficiency / Q000378:metabolism
D053523:Amelogenin; C507201:Amelx protein, rat; D003746:Dental Enamel Proteins; D012333:RNA, Messenger; D002117:Calcitriol