Transcriptional Factor ATF6 is Involved in Odontoblastic Differentiation

Abstract

ATF6 is an endoplasmic reticulum (ER) membrane-bound transcription factor that regulates various cellular functions. The purpose of this study was to investigate the role of ATF6 in odontoblast differentiation. Rat tooth germs were isolated, changes in gene expression were evaluated over time, and localization of ATF6 was determined by immunohistochemistry. Human dental pulp cells (HDPCs) were cultured with 50 µg/mL ascorbic acid and 5 mmol/L β-glycerophosphate or 100 ng/mL bone morphogenetic protein 2 to induce differentiation. Translocation of ATF6 was observed by immunofluorescence and confocal microscopy. Overexpression of ATF6 was performed with an adenoviral vector. Matrix mineralization was evaluated by alizarin red staining. Immunoreactivity to anti-ATF6 was observed in the odontoblastic layer of the molar tooth germ, and expressions of ATF6, dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP1) increased gradually during tooth germ development. When HDPCs were cultured in differentiation media, ATF6, DSPP, and DMP1 expression increased with the expression of unfolded protein response (UPR) markers, BiP and CHOP. Immunofluorescence results showed that ATF6 protein moved from cytoplasm to nucleus when cells were exposed to differentiation media. Notably, overexpression of ATF6 increased DSPP and DMP1 expression, alkaline phosphatase (ALP) activity, and matrix mineralization in HDPC cultures. Inhibition of ATF6 decreased ALP activity and mineralization. These results suggest that ER membrane-bound transcriptional factor ATF6 may be involved in odontoblastic differentiation.

Expression of Pannexin3 in human odontoblast-like cells and its hemichannel function in mediating ATP release

“…Panx3 was detected primarily in odontoblast layer. DSP, which has been shown in developmental stages of tooth germ, 40 was found in odontoblast, predentin and dentinal tubular layer.…”

SP1 promotes the odontoblastic differentiation of dental papilla cells

“…A variety of transcription factors have been previously studied to reveal the molecular mechanisms under the odontoblastic differentiation of DPCs (Kim et al . ; Kuzynski et al . ; Yang et al .…”

Mineral trioxide aggregate induces osteoblastogenesis via Atf6

“…Moreover, p50 the activated form Atf6 was dose-dependently increased by addition of MTA. Because Atf6 plays an important role of differentiation in both odontoblast (Kim et al, 2014) and osteoblast (Jang et al, 2012), we examined whether Atf6 is the candidate “MTA activated transcription factor” to induce osteoblastic differentiation. As expected, MTA induced Bglap mRNA expression in a BMP-2-independent manner.…”