Bcl11b regulates enamel matrix protein expression and dental epithelial cell differentiation during rat tooth development

Li,Ziyue; Chen,Guoqing; Yang,Yaling; Guo,Weihua; Tian,Weidong

doi:10.3892/mmr.2016.6030

Bcl11b regulates enamel matrix protein expression and dental epithelial cell differentiation during rat tooth development

Authors:
- Ziyue Li
- Guoqing Chen
- Yaling Yang
- Weihua Guo
- Weidong Tian
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Affiliations: National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: December 12, 2016 https://doi.org/10.3892/mmr.2016.6030
Pages: 297-304

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Abstract

Amelogenesis, beginning with thickened epithelial aggregation and ending with highly mineralized enamel formation, is a process mediated by a complex signaling network that involves several molecules, including growth and transcription factors. During early tooth development, the transcription factor B‑cell CLL/lymphoma 11B (Bcl11b) participates in dental epithelial cell proliferation and differentiation. However, whether it affects the postnatal regulation of enamel matrix protein expression and ameloblast differentiation remains unclear. To clarify the role of Bcl11b in enamel development, the present study initially detected the protein expression levels of Bcl11b during tooth development using immunohistochemistry, from the embryonic lamina stage to the postnatal period, and demonstrated that Bcl11b is predominantly restricted to cervical loop epithelial cells at the cap and bell stages, whereas expression is reduced in ameloblasts. Notably, the expression pattern of Bcl11b during tooth development differed between rats and mice. Knockdown of Bcl11b by specific small interfering RNA attenuated the expression of enamel‑associated genes, including amelogenin, X‑linked (Amelx), ameloblastin (Ambn), enamelin (Enam), kallikrein related peptidase 4 (Klk4), matrix metallopeptidase 20 and Msh homeobox 2 (Msx2). Chromatin immunoprecipitation assay verified that Msx2 was a transcriptional target of Bcl11b. However, overexpression of Msx2 resulted in downregulation of enamel‑associated genes, including Ambn, Amelx, Enam and Klk4. The present study suggested that Bcl11b serves a potentially important role in the regulation of ameloblast differentiation and enamel matrix protein expression. In addition, a complex feedback regulatory network may exist between Bcl11b and Msx2.

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