Regulation of odontoblast differentiation by Cpne7, a dental epithelium-derived factor, via the Runx2–Nfic–Osx–Dspp pathway

다국어 초록 (Multilingual Abstract)

Tooth development involves complex epithelial–mesenchymal interactions. In previous studies, disruption of these interactions was observed in nuclear factor I-C (Nfic)-deficient mouse incisors. Cpne7, a preameloblast-derived factor that can induce the promoter activity of the odontogenic marker dentin sialophosphoprotein (DSPP), was identified in a recent study. However, its relationship with the Nfic-mediated odontogenic pathway is unknown.
To confirm the odontogenic ability of epithelial factors, MDPC-23 odontoblastic cells were cultured in a preameloblast-conditioned medium (PA-CM) obtained from mouse apical bud cells. The effects of dental epithelium on odontoblast differentiation were compared by culturing WT and Nfic−/− mouse incisor and molar primary pulp cells. To investigate the role of Cpne7 in the odontogenic signaling pathway, MDPC-23 cells were grown in PA-CM with CPNE7-Ab, and human dental pulp cells (hDPCs) were treated with recombinant Cpne7 (rCPNE7). Then, the expression of odontoblast-related genes was analyzed.
Histological analysis of Nfic−/− mouse incisors revealed strong expression of RUNX2 in abnormal hard tissues adjacent to the dental epithelium, whereas the expression of OSX was not detected. Increased levels of Runx2 and down-regulation of Osx and Dspp were detected in Nfic−/− mouse incisor pulp cells, whereas no significant change was observed in molar pulp cells. In MDPC-23 cells, inactivation of Cpne7 in PA-CM inhibited the stimulatory effect of PA-CM on Runx2 and Osx. rCPNE7 treatment of hDPCs produced elevated levels of Osx, Dmp1, and Dspp.
These findings suggest that the dental epithelial factor Cpne7 controls odontoblast differentiation of dental mesenchymal cells by inducing the Runx2–Nfic–Osx–Dspp signaling pathway.

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