title: TGF-ß regulates enamel mineralization and maturation through KLK4 expression.
abstract: Transforming growth factor-ß (TGF-ß) 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-ß signaling during amelogenesis, we developed a transgenic mouse line that harbors bovine amelogenin promoter-driven Cre recombinase, and bred this line with TGF-ß receptor II floxed mice to generate ameloblast-specific TGF-ß 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-ß signaling through the expression of KLK4. Thus, our study indicates that TGF-ß signaling plays an important role in ameloblast functions and enamel maturation.
authors.affiliation: Gene Transfer Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Cho
authors.forename: Naoto
authors.initials: N
authors.lastname: Haruyama
authors.forename: Bradford
authors.initials: B
authors.lastname: Hall
authors.forename: Mary Jo S
authors.initials: MJ
authors.lastname: Danton
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Praveen
authors.initials: P
authors.lastname: Arany
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
authors.forename: Yassine
authors.initials: Y
authors.lastname: Harichane
authors.forename: Michel
authors.initials: M
authors.lastname: Goldberg
authors.forename: Carolyn W
authors.initials: CW
authors.lastname: Gibson
authors.forename: Ashok B
authors.initials: AB
authors.lastname: Kulkarni
mesh_terms: D000818:Animals; D003743:Dental Enamel / Q000502:physiology*; D007610:Kallikreins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D060888:Real-Time Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000502:physiology*; D055114:X-Ray Microtomography
chemical_list: D016212:Transforming Growth Factor beta; D007610:Kallikreins; C120801:kallikrein 4