Abstract
Tooth development is a progressive process regulated by interactions between epithelial and mesenchymal tissues. Our previous studies showed that copine-7 (Cpne7), a dental epithelium-derived protein, is a signalling molecule that is secreted by preameloblasts and regulates the differentiation of preodontoblasts into odontoblasts. However, the mechanisms involved in the translocation of Cpne7 from preameloblasts to preodontoblasts and the functions of Cpne7 during odontogenesis are poorly understood. Here, we showed that the internalization of Cpne7 was mediated primarily by caveolae. This process was initiated by Cpne7 binding to the cell surface protein, nucleolin. Treatment with recombinant Cpne7 protein (rCpne7) in human dental pulp cells (hDPCs) caused an increase in the number of ciliated cells. The expression level of cilium components, Ift88 and Kif3a, and Dspp were increased by rCpne7. Treatment with Ift88 siRNA in hDPCs and MDPC-23 cells significantly down-regulated the expression of Dspp, an odontoblastic differentiation marker gene. Furthermore, the treatment with nucleolin siRNA in MDPC-23 cells decreased the expression of Dmp1, Dspp, and cilium components. Our findings suggested that the binding of Cpne7 with its receptor, nucleolin, has an important function involving Cpne7 internalization into preodontoblasts and regulation of Dspp expression through ciliogenesis during odontoblast differentiation.
Highlights
Tooth development is a consequence of programmed, sequential, and reciprocal communications between the dental epithelium and mesenchyme, which is mediated by specific temporal-spatial expression of a series of genes[1]
Based on the concept of epithelial-mesenchymal interactions during odontogenesis, we previously investigated the effects of preameloblast-conditioned medium (PA-CM) on the odontogenic differentiation of human dental pulp cells
To assess whether the presence of primary cilium components had any physiological relevance in odontoblast differentiation, we examined the number of primary cilia and the expression of cilium components during odontoblast differentiation using immunofluorescence microscopy and real-time PCR
Summary
Tooth development is a consequence of programmed, sequential, and reciprocal communications between the dental epithelium and mesenchyme, which is mediated by specific temporal-spatial expression of a series of genes[1]. Epithelial and mesenchymal cells differentiate into ameloblasts and odontoblasts, respectively, during crown formation[2]. This study reported that epithelial signals induced in the mesenchyme led to subsequent odontoblast differentiation and dentin formation. Based on the concept of epithelial-mesenchymal interactions during odontogenesis, we previously investigated the effects of preameloblast-conditioned medium (PA-CM) on the odontogenic differentiation of human dental pulp cells (hDPCs). There have been few studies of the functions of Cpne[7] besides our previous report that Cpne[7], a diffusing signalling molecule, is a regulator of the differentiation of mesenchymal cells into odontoblasts. The molecular mechanisms responsible for inducing cilianogenesis during odontogenesis remain unclear
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