TGF-β regulates enamel mineralization and maturation through KLK4 expression

Andrew Cho, Naoto Haruyama, Bradford Hall, Mary Jo S. Danton, Lu Zhang, Praveen Arany, David J. Mooney, Yassine Harichane, Michel Goldberg, Carolyn W. Gibson, Ashok B. Kulkarni

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


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.

Original languageEnglish
Article numbere82267
JournalPloS one
Issue number11
Publication statusPublished - Nov 20 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General


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