TY - JOUR
T1 - Claudin-16 Deficiency Impairs Tight Junction Function in Ameloblasts, Leading to Abnormal Enamel Formation
AU - Bardet, Claire
AU - Courson, Frédéric
AU - Wu, Yong
AU - Khaddam, Mayssam
AU - Salmon, Benjamin
AU - Ribes, Sandy
AU - Thumfart, Julia
AU - Yamaguti, Paulo M.
AU - Rochefort, Gael Y.
AU - Figueres, Marie Lucile
AU - Breiderhoff, Tilman
AU - Garcia-Castaño, Alejandro
AU - Vallée, Benoit
AU - Le Denmat, Dominique
AU - Baroukh, Brigitte
AU - Guilbert, Thomas
AU - Schmitt, Alain
AU - Massé, Jean Marc
AU - Bazin, Dominique
AU - Lorenz, Georg
AU - Morawietz, Maria
AU - Hou, Jianghui
AU - Carvalho-Lobato, Patricia
AU - Manzanares, Maria Cristina
AU - Fricain, Jean Christophe
AU - Talmud, Deborah
AU - Demontis, Renato
AU - Neves, Francisco
AU - Zenaty, Delphine
AU - Berdal, Ariane
AU - Kiesow, Andreas
AU - Petzold, Matthias
AU - Menashi, Suzanne
AU - Linglart, Agnes
AU - Acevedo, Ana Carolina
AU - Vargas-Poussou, Rosa
AU - Müller, Dominik
AU - Houillier, Pascal
AU - Chaussain, Catherine
N1 - Publisher Copyright:
© 2015 American Society for Bone and Mineral Research.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - Claudin-16 protein (CLDN16) is a component of tight junctions (TJ) with a restrictive distribution so far demonstrated mainly in the kidney. Here, we demonstrate the expression of CLDN16 also in the tooth germ and show that claudin-16 gene (CLDN16) mutations result in amelogenesis imperfecta (AI) in the 5 studied patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). To investigate the role of CLDN16 in tooth formation, we studied a murine model of FHHNC and showed that CLDN16 deficiency led to altered secretory ameloblast TJ structure, lowering of extracellular pH in the forming enamel matrix, and abnormal enamel matrix protein processing, resulting in an enamel phenotype closely resembling human AI. This study unravels an association of FHHNC owing to CLDN16 mutations with AI, which is directly related to the loss of function of CLDN16 during amelogenesis. Overall, this study indicates for the first time the importance of a TJ protein in tooth formation and underlines the need to establish a specific dental follow-up for these patients.
AB - Claudin-16 protein (CLDN16) is a component of tight junctions (TJ) with a restrictive distribution so far demonstrated mainly in the kidney. Here, we demonstrate the expression of CLDN16 also in the tooth germ and show that claudin-16 gene (CLDN16) mutations result in amelogenesis imperfecta (AI) in the 5 studied patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). To investigate the role of CLDN16 in tooth formation, we studied a murine model of FHHNC and showed that CLDN16 deficiency led to altered secretory ameloblast TJ structure, lowering of extracellular pH in the forming enamel matrix, and abnormal enamel matrix protein processing, resulting in an enamel phenotype closely resembling human AI. This study unravels an association of FHHNC owing to CLDN16 mutations with AI, which is directly related to the loss of function of CLDN16 during amelogenesis. Overall, this study indicates for the first time the importance of a TJ protein in tooth formation and underlines the need to establish a specific dental follow-up for these patients.
KW - AMELOGENESIS IMPERFECTA (AI)
KW - FAMILIAL HYPOMAGNESEMIA WITH HYPERCALCIURIA AND NEPHROCALCINOSIS (FHHNC)
KW - MMP-20
KW - SECRETORY AMELOBLASTS
KW - pH
UR - https://www.scopus.com/pages/publications/84951173557
U2 - 10.1002/jbmr.2726
DO - 10.1002/jbmr.2726
M3 - Article
C2 - 26426912
AN - SCOPUS:84951173557
SN - 0884-0431
VL - 31
SP - 498
EP - 513
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 3
ER -