Thymosin beta 4 is associated with RUNX2 expression through the Smad and Akt signaling pathways in mouse dental epithelial cells

Hirotaka Someya, Hiroaki Fujiwara, Kengo Nagata, Hiroko Wada, Kana Hasegawa, Yurie Mikami, Akiko Jinno, Hidetaka Sakai, Kiyoshi Koyano, Tamotsu Kiyoshima

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

In previous studies by our group, we reported that thymosin beta 4 (Tb4) is closely associated with the initiation and development of the tooth germ, and can induce the expression of runt-related transcription factor 2 (RUNX2) during the development of the tooth germ. RUNX2 regulates the expression of odontogenesis-related genes, such as amelogenin, X-linked (Amelx), ameloblastin (Ambn) and enamelin (Enam), as well as the differentiation of osteoblasts during bone formation. However, the mechanisms through which Tb4 induces the expression of RUNX2 remain unknown. In the present study, we employed a mouse dental epithelial cell line, mDE6, with the aim to elucidate these mechanisms. The mDE6 cells expressed odontogenesis-related genes, such as Runx2, Amelx, Ambn and Enam, and formed calcified matrices upon the induction of calcification, thus showing characteristics of odontogenic epithelial cells. The expression of odontogenesis-related genes, and the calcification of the mDE6 cells were reduced by the inhibition of phosphorylated Smad1/5 (p-Smad1/5) and phosphorylated Akt (p-Akt) proteins. Furthermore, we used siRNA against Tb4 to determine whether RUNX2 expression and calcifcation are associated with Tb4 expression in the mDE6 cells. The protein expression of p-Smad1/5 and p-Akt in the mDE6 cells was reduced by treatment with Tb4-siRNA. These results suggest that Tb4 is associated with RUNX2 expression through the Smad and PI3K-Akt signaling pathways, and with calcification through RUNX2 expression in the mDE6 cells. This study provides putative information concerning the signaling pathway through which Tb4 induces RUNX2 expression, which may help to understand the regulation of tooth development and tooth regeneration.

Original languageEnglish
Pages (from-to)1169-1178
Number of pages10
JournalInternational journal of molecular medicine
Volume35
Issue number5
DOIs
Publication statusPublished - May 1 2015

Fingerprint

Tooth
Epithelial Cells
Odontogenesis
Amelogenin
Tooth Germ
Small Interfering RNA
Genes
thymosin beta(4)
Osteoblasts
Phosphatidylinositol 3-Kinases
Osteogenesis
Regeneration
Proteins
Transcription Factors
Cell Line
tuftelin

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Thymosin beta 4 is associated with RUNX2 expression through the Smad and Akt signaling pathways in mouse dental epithelial cells. / Someya, Hirotaka; Fujiwara, Hiroaki; Nagata, Kengo; Wada, Hiroko; Hasegawa, Kana; Mikami, Yurie; Jinno, Akiko; Sakai, Hidetaka; Koyano, Kiyoshi; Kiyoshima, Tamotsu.

In: International journal of molecular medicine, Vol. 35, No. 5, 01.05.2015, p. 1169-1178.

Research output: Contribution to journalArticle

@article{a008e2e709b844759af364cc054e159d,
title = "Thymosin beta 4 is associated with RUNX2 expression through the Smad and Akt signaling pathways in mouse dental epithelial cells",
abstract = "In previous studies by our group, we reported that thymosin beta 4 (Tb4) is closely associated with the initiation and development of the tooth germ, and can induce the expression of runt-related transcription factor 2 (RUNX2) during the development of the tooth germ. RUNX2 regulates the expression of odontogenesis-related genes, such as amelogenin, X-linked (Amelx), ameloblastin (Ambn) and enamelin (Enam), as well as the differentiation of osteoblasts during bone formation. However, the mechanisms through which Tb4 induces the expression of RUNX2 remain unknown. In the present study, we employed a mouse dental epithelial cell line, mDE6, with the aim to elucidate these mechanisms. The mDE6 cells expressed odontogenesis-related genes, such as Runx2, Amelx, Ambn and Enam, and formed calcified matrices upon the induction of calcification, thus showing characteristics of odontogenic epithelial cells. The expression of odontogenesis-related genes, and the calcification of the mDE6 cells were reduced by the inhibition of phosphorylated Smad1/5 (p-Smad1/5) and phosphorylated Akt (p-Akt) proteins. Furthermore, we used siRNA against Tb4 to determine whether RUNX2 expression and calcifcation are associated with Tb4 expression in the mDE6 cells. The protein expression of p-Smad1/5 and p-Akt in the mDE6 cells was reduced by treatment with Tb4-siRNA. These results suggest that Tb4 is associated with RUNX2 expression through the Smad and PI3K-Akt signaling pathways, and with calcification through RUNX2 expression in the mDE6 cells. This study provides putative information concerning the signaling pathway through which Tb4 induces RUNX2 expression, which may help to understand the regulation of tooth development and tooth regeneration.",
author = "Hirotaka Someya and Hiroaki Fujiwara and Kengo Nagata and Hiroko Wada and Kana Hasegawa and Yurie Mikami and Akiko Jinno and Hidetaka Sakai and Kiyoshi Koyano and Tamotsu Kiyoshima",
year = "2015",
month = "5",
day = "1",
doi = "10.3892/ijmm.2015.2118",
language = "English",
volume = "35",
pages = "1169--1178",
journal = "International Journal of Molecular Medicine",
issn = "1107-3756",
publisher = "Spandidos Publications",
number = "5",

}

TY - JOUR

T1 - Thymosin beta 4 is associated with RUNX2 expression through the Smad and Akt signaling pathways in mouse dental epithelial cells

AU - Someya, Hirotaka

AU - Fujiwara, Hiroaki

AU - Nagata, Kengo

AU - Wada, Hiroko

AU - Hasegawa, Kana

AU - Mikami, Yurie

AU - Jinno, Akiko

AU - Sakai, Hidetaka

AU - Koyano, Kiyoshi

AU - Kiyoshima, Tamotsu

PY - 2015/5/1

Y1 - 2015/5/1

N2 - In previous studies by our group, we reported that thymosin beta 4 (Tb4) is closely associated with the initiation and development of the tooth germ, and can induce the expression of runt-related transcription factor 2 (RUNX2) during the development of the tooth germ. RUNX2 regulates the expression of odontogenesis-related genes, such as amelogenin, X-linked (Amelx), ameloblastin (Ambn) and enamelin (Enam), as well as the differentiation of osteoblasts during bone formation. However, the mechanisms through which Tb4 induces the expression of RUNX2 remain unknown. In the present study, we employed a mouse dental epithelial cell line, mDE6, with the aim to elucidate these mechanisms. The mDE6 cells expressed odontogenesis-related genes, such as Runx2, Amelx, Ambn and Enam, and formed calcified matrices upon the induction of calcification, thus showing characteristics of odontogenic epithelial cells. The expression of odontogenesis-related genes, and the calcification of the mDE6 cells were reduced by the inhibition of phosphorylated Smad1/5 (p-Smad1/5) and phosphorylated Akt (p-Akt) proteins. Furthermore, we used siRNA against Tb4 to determine whether RUNX2 expression and calcifcation are associated with Tb4 expression in the mDE6 cells. The protein expression of p-Smad1/5 and p-Akt in the mDE6 cells was reduced by treatment with Tb4-siRNA. These results suggest that Tb4 is associated with RUNX2 expression through the Smad and PI3K-Akt signaling pathways, and with calcification through RUNX2 expression in the mDE6 cells. This study provides putative information concerning the signaling pathway through which Tb4 induces RUNX2 expression, which may help to understand the regulation of tooth development and tooth regeneration.

AB - In previous studies by our group, we reported that thymosin beta 4 (Tb4) is closely associated with the initiation and development of the tooth germ, and can induce the expression of runt-related transcription factor 2 (RUNX2) during the development of the tooth germ. RUNX2 regulates the expression of odontogenesis-related genes, such as amelogenin, X-linked (Amelx), ameloblastin (Ambn) and enamelin (Enam), as well as the differentiation of osteoblasts during bone formation. However, the mechanisms through which Tb4 induces the expression of RUNX2 remain unknown. In the present study, we employed a mouse dental epithelial cell line, mDE6, with the aim to elucidate these mechanisms. The mDE6 cells expressed odontogenesis-related genes, such as Runx2, Amelx, Ambn and Enam, and formed calcified matrices upon the induction of calcification, thus showing characteristics of odontogenic epithelial cells. The expression of odontogenesis-related genes, and the calcification of the mDE6 cells were reduced by the inhibition of phosphorylated Smad1/5 (p-Smad1/5) and phosphorylated Akt (p-Akt) proteins. Furthermore, we used siRNA against Tb4 to determine whether RUNX2 expression and calcifcation are associated with Tb4 expression in the mDE6 cells. The protein expression of p-Smad1/5 and p-Akt in the mDE6 cells was reduced by treatment with Tb4-siRNA. These results suggest that Tb4 is associated with RUNX2 expression through the Smad and PI3K-Akt signaling pathways, and with calcification through RUNX2 expression in the mDE6 cells. This study provides putative information concerning the signaling pathway through which Tb4 induces RUNX2 expression, which may help to understand the regulation of tooth development and tooth regeneration.

UR - http://www.scopus.com/inward/record.url?scp=84925459723&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925459723&partnerID=8YFLogxK

U2 - 10.3892/ijmm.2015.2118

DO - 10.3892/ijmm.2015.2118

M3 - Article

C2 - 25739055

AN - SCOPUS:84925459723

VL - 35

SP - 1169

EP - 1178

JO - International Journal of Molecular Medicine

JF - International Journal of Molecular Medicine

SN - 1107-3756

IS - 5

ER -