Globoside accelerates the differentiation of dental epithelial cells into ameloblasts.

Takashi Nakamura,Hidemitsu Harada,Yuta Chiba,Kan Saito,Satoshi Fukumoto,Masahiro Naruse

doi:10.1038/ijos.2016.35

Abstract

Tooth crown morphogenesis is tightly regulated by the proliferation and differentiation of dental epithelial cells. Globoside (Gb4), a globo-series glycosphingolipid, is highly expressed during embryogenesis as well as organogenesis, including tooth development. We previously reported that Gb4 is dominantly expressed in the neutral lipid fraction of dental epithelial cells. However, because its functional role in tooth development remains unknown, we investigated the involvement of Gb4 in dental epithelial cell differentiation. The expression of Gb4 was detected in ameloblasts of postnatal mouse molars and incisors. A cell culture analysis using HAT-7 cells, a rat-derived dental epithelial cell line, revealed that Gb4 did not promote dental epithelial cell proliferation. Interestingly, exogenous administration of Gb4 enhanced the gene expression of enamel extracellular matrix proteins such as ameloblastin, amelogenin, and enamelin in dental epithelial cells as well as in developing tooth germs. Gb4 also induced the expression of TrkB, one of the key receptors required for ameloblast induction in dental epithelial cells. In contrast, Gb4 downregulated the expression of p75, a receptor for neurotrophins (including neurotrophin-4) and a marker of undifferentiated dental epithelial cells. In addition, we found that exogenous administration of Gb4 to dental epithelial cells stimulated the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase signalling pathways. Furthermore, Gb4 induced the expression of epiprofin and Runx2, the positive regulators for ameloblastin gene transcription. Thus, our results suggest that Gb4 contributes to promoting the differentiation of dental epithelial cells into ameloblasts.

Highlights

IntroductionInteractions between dental epithelial and mesenchymal cells play important roles in cell proliferation and differentiation to regulate the size and shape of a tooth.[1] A variety of growth factors and their receptors are involved in these interactions,[2] and the morphological formation of the tooth crown is precisely regulated by a balance between the proliferation and differentiation of dental epithelial cells.[3] Enamel, the hardest structure in the human body, covers the entire tooth surface to prevent attrition
During tooth development, interactions between dental epithelial and mesenchymal cells play important roles in cell proliferation and differentiation to regulate the size and shape of a tooth.[1]
These results suggest that Gb4 is expressed in dental epithelial cells and is colocalized with Ambn, a marker of ameloblast differentiation

Summary

Introduction

Interactions between dental epithelial and mesenchymal cells play important roles in cell proliferation and differentiation to regulate the size and shape of a tooth.[1] A variety of growth factors and their receptors are involved in these interactions,[2] and the morphological formation of the tooth crown is precisely regulated by a balance between the proliferation and differentiation of dental epithelial cells.[3] Enamel, the hardest structure in the human body, covers the entire tooth surface to prevent attrition. The transcription factor Runx[2] ( called Cbfa1), known for its critical role in osteoblast differentiation, has been shown to regulate Ambn gene transcription by binding to the osteoblast-specific element in the proximal Ambn promoter region.[18]

Methods

Results

Conclusion