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

Someya H, Fujiwara H, Nagata K, Wada H, Hasegawa K, Mikami Y, Jinno A, Sakai H, Koyano K, Kiyoshima T - Int. J. Mol. Med. (2015)

Bottom Line: 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.The protein expression of p-Smad1/5 and p-Akt in the mDE6 cells was reduced by treatment with Tb4-siRNA.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.

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 calcification 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.

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Schematic illustration of the putative signaling pathways from thymosin beta 4 (Tb4) to runt-related transcription factor 2 (RUNX2) in the mDE6 cells. Several signaling pathways through Smad, PI3K-Akt, MAPK and/or Wnt/β-catenin have been reported to be upstream of RUNX2 expression. The results of this study suggest that Smad and PI3K-Akt may participate in Tb4-RUNX2 signaling pathway(s) in the mDE6 cells. Tb4 may increase RUNX2 expression to induce the expression of odontogenesis-related genes in the mDE6 cells. The black arrows indicate putative Tb4-RUNX2 signaling pathways revealed in this study, while the dotted arrows indicate possible Tb4-RUNX2 signaling pathways that were not supported in this study. The gray arrows indicate signaling pathways reported in previous studies [(A) (34,42); (B) (34,43); (C) (34,44); (D) 34,45; (E) (9,17,19,29–31)]. RUNX2 can upregulate the expression of downstream biological effectors, including odontogenesis-related genes and calcification-related factors.
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f6-ijmm-35-05-1169: Schematic illustration of the putative signaling pathways from thymosin beta 4 (Tb4) to runt-related transcription factor 2 (RUNX2) in the mDE6 cells. Several signaling pathways through Smad, PI3K-Akt, MAPK and/or Wnt/β-catenin have been reported to be upstream of RUNX2 expression. The results of this study suggest that Smad and PI3K-Akt may participate in Tb4-RUNX2 signaling pathway(s) in the mDE6 cells. Tb4 may increase RUNX2 expression to induce the expression of odontogenesis-related genes in the mDE6 cells. The black arrows indicate putative Tb4-RUNX2 signaling pathways revealed in this study, while the dotted arrows indicate possible Tb4-RUNX2 signaling pathways that were not supported in this study. The gray arrows indicate signaling pathways reported in previous studies [(A) (34,42); (B) (34,43); (C) (34,44); (D) 34,45; (E) (9,17,19,29–31)]. RUNX2 can upregulate the expression of downstream biological effectors, including odontogenesis-related genes and calcification-related factors.

Mentions: The data from our study indicate the putative signaling pathways from Tb4 to Runx2 expression in the mDE6 cells. The Smad and PI3K-Akt signaling pathways also appeared to play a role in the Tb4-RUNX2 pathway in mDE6 cells (Fig. 6). However, little is known as to whether upregulated Tb4 can induce the expression of odontogenesis-related genes, such as Amelx, Ambn and Enam, without the expression of Runx2, and of the association between Tb4 and other signaling pathways upstream of Runx2 expression.


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

Someya H, Fujiwara H, Nagata K, Wada H, Hasegawa K, Mikami Y, Jinno A, Sakai H, Koyano K, Kiyoshima T - Int. J. Mol. Med. (2015)

Schematic illustration of the putative signaling pathways from thymosin beta 4 (Tb4) to runt-related transcription factor 2 (RUNX2) in the mDE6 cells. Several signaling pathways through Smad, PI3K-Akt, MAPK and/or Wnt/β-catenin have been reported to be upstream of RUNX2 expression. The results of this study suggest that Smad and PI3K-Akt may participate in Tb4-RUNX2 signaling pathway(s) in the mDE6 cells. Tb4 may increase RUNX2 expression to induce the expression of odontogenesis-related genes in the mDE6 cells. The black arrows indicate putative Tb4-RUNX2 signaling pathways revealed in this study, while the dotted arrows indicate possible Tb4-RUNX2 signaling pathways that were not supported in this study. The gray arrows indicate signaling pathways reported in previous studies [(A) (34,42); (B) (34,43); (C) (34,44); (D) 34,45; (E) (9,17,19,29–31)]. RUNX2 can upregulate the expression of downstream biological effectors, including odontogenesis-related genes and calcification-related factors.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4380193&req=5

f6-ijmm-35-05-1169: Schematic illustration of the putative signaling pathways from thymosin beta 4 (Tb4) to runt-related transcription factor 2 (RUNX2) in the mDE6 cells. Several signaling pathways through Smad, PI3K-Akt, MAPK and/or Wnt/β-catenin have been reported to be upstream of RUNX2 expression. The results of this study suggest that Smad and PI3K-Akt may participate in Tb4-RUNX2 signaling pathway(s) in the mDE6 cells. Tb4 may increase RUNX2 expression to induce the expression of odontogenesis-related genes in the mDE6 cells. The black arrows indicate putative Tb4-RUNX2 signaling pathways revealed in this study, while the dotted arrows indicate possible Tb4-RUNX2 signaling pathways that were not supported in this study. The gray arrows indicate signaling pathways reported in previous studies [(A) (34,42); (B) (34,43); (C) (34,44); (D) 34,45; (E) (9,17,19,29–31)]. RUNX2 can upregulate the expression of downstream biological effectors, including odontogenesis-related genes and calcification-related factors.
Mentions: The data from our study indicate the putative signaling pathways from Tb4 to Runx2 expression in the mDE6 cells. The Smad and PI3K-Akt signaling pathways also appeared to play a role in the Tb4-RUNX2 pathway in mDE6 cells (Fig. 6). However, little is known as to whether upregulated Tb4 can induce the expression of odontogenesis-related genes, such as Amelx, Ambn and Enam, without the expression of Runx2, and of the association between Tb4 and other signaling pathways upstream of Runx2 expression.

Bottom Line: 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.The protein expression of p-Smad1/5 and p-Akt in the mDE6 cells was reduced by treatment with Tb4-siRNA.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.

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 calcification 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.

Show MeSH
Related in: MedlinePlus