Loss of transforming growth factor-β1 in epithelium cells affects enamel formation in mice

Arch Oral Biol. 2018 Dec:96:146-154. doi: 10.1016/j.archoralbio.2018.09.003. Epub 2018 Sep 12.

Abstract

Objectives: In order to understand the specific in vivo function of transforming growth factor-beta1 (TGF-β1), we successfully established aTGF-β1 deficient mouse model using a conditional knockout method. In the present study, we aimed to further understand the potential role of TGF-β1 in enamel formation.

Design: Transgenic mice withoutTGF-β1 in epithelial cells were generated. Scanning electron microscopy and micro-computed tomography analysis were used to detect the dental appearance, enamel microstructure and tooth density. Histological analysis was used to examine the residual organic matrix of enamel. Quantitative real-time polymerase chain reaction was used to analyze the expressions of enamel matrix proteins at the mRNA level.

Results: The enamel of mandibular molars and incisors inTGF-β1 conditional knockout mice displayed severe attrition and lower density compared with the wild-type littermates. A slender microstructure of enamel rod was observed, and enamel matrix proteins were retained in the enamel space at the maturation stage in conditional knockout mice. Moreover, the expressions of enamel matrix protein-encoding genes, such as amelogenin (Amelx), ameloblastin (Ambn), Enamelin (Enam) and matrix metalloproteinase-20 (Mmp-20), were increased in enamel organs of conditional knockout mice. On the other hand, the expressions of Amelotin (Amtn), kallikrein-related peptidase-4 (Klk4), C4orf26 and WD repeat-containing protein 72 (Wdr72) were dramatically decreased at the transition and maturation stages.

Conclusions: TGF-β1 played an important role in enamel mineralization through decreasing synthesis ofAmelx, Ambn and Enam and increasing synthesis of Klk4, Amtn, Corf26 and Wdr72.

Keywords: Ameloblasts; Conditional knockout; Enamel matrix protein; Enamel mineralization; Transforming growth factor-beta1.

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Enamel Organ / cytology
  • Enamel Organ / metabolism*
  • Epithelial Cells / metabolism*
  • Mice
  • Mice, Transgenic
  • Microscopy, Electron, Scanning
  • Real-Time Polymerase Chain Reaction
  • Transforming Growth Factor beta1 / metabolism*
  • X-Ray Microtomography

Substances

  • Transforming Growth Factor beta1