TY - JOUR
T1 - TGF-β regulates enamel mineralization and maturation through KLK4 expression
AU - Cho, Andrew
AU - Haruyama, Naoto
AU - Hall, Bradford
AU - Danton, Mary Jo S.
AU - Zhang, Lu
AU - Arany, Praveen
AU - Mooney, David J.
AU - Harichane, Yassine
AU - Goldberg, Michel
AU - Gibson, Carolyn W.
AU - Kulkarni, Ashok B.
PY - 2013/11/20
Y1 - 2013/11/20
N2 - Transforming growth factor-β (TGF-β) signaling plays an important role in regulating crucial biological processes such as cell proliferation, differentiation, apoptosis, and extracellular matrix remodeling. Many of these processes are also an integral part of amelogenesis. In order to delineate a precise role of TGF-β signaling during amelogenesis, we developed a transgenic mouse line that harbors bovine amelogenin promoter-driven Cre recombinase, and bred this line with TGF-β receptor II floxed mice to generate ameloblast-specific TGF-β receptor II conditional knockout (cKO) mice. Histological analysis of the teeth at postnatal day 7 (P7) showed altered enamel matrix composition in the cKO mice as compared to the floxed mice that had enamel similar to the wild-type mice. The μCT and SEM analyses revealed decreased mineral content in the cKO enamel concomitant with increased attrition and thinner enamel crystallites. Although the mRNA levels remained unaltered, immunostaining revealed increased amelogenin, ameloblastin, and enamelin localization in the cKO enamel at the maturation stage. Interestingly, KLK4 mRNA levels were significantly reduced in the cKO teeth along with a slight increase in MMP-20 levels, suggesting that normal enamel maturation is regulated by TGF-β signaling through the expression of KLK4. Thus, our study indicates that TGF-β signaling plays an important role in ameloblast functions and enamel maturation.
AB - Transforming growth factor-β (TGF-β) signaling plays an important role in regulating crucial biological processes such as cell proliferation, differentiation, apoptosis, and extracellular matrix remodeling. Many of these processes are also an integral part of amelogenesis. In order to delineate a precise role of TGF-β signaling during amelogenesis, we developed a transgenic mouse line that harbors bovine amelogenin promoter-driven Cre recombinase, and bred this line with TGF-β receptor II floxed mice to generate ameloblast-specific TGF-β receptor II conditional knockout (cKO) mice. Histological analysis of the teeth at postnatal day 7 (P7) showed altered enamel matrix composition in the cKO mice as compared to the floxed mice that had enamel similar to the wild-type mice. The μCT and SEM analyses revealed decreased mineral content in the cKO enamel concomitant with increased attrition and thinner enamel crystallites. Although the mRNA levels remained unaltered, immunostaining revealed increased amelogenin, ameloblastin, and enamelin localization in the cKO enamel at the maturation stage. Interestingly, KLK4 mRNA levels were significantly reduced in the cKO teeth along with a slight increase in MMP-20 levels, suggesting that normal enamel maturation is regulated by TGF-β signaling through the expression of KLK4. Thus, our study indicates that TGF-β signaling plays an important role in ameloblast functions and enamel maturation.
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U2 - 10.1371/journal.pone.0082267
DO - 10.1371/journal.pone.0082267
M3 - Article
C2 - 24278477
AN - SCOPUS:84896733103
SN - 1932-6203
VL - 8
JO - PloS one
JF - PloS one
IS - 11
M1 - e82267
ER -