Int J Biol Sci 2012; 8(7):1062-1074. doi:10.7150/ijbs.4488 This issue Cite

Research Paper

TGF-β-Operated Growth Inhibition and Translineage Commitment into Smooth Muscle Cells of Periodontal Ligament-Derived Endothelial Progenitor Cells through Smad- and p38 MAPK-Dependent Signals

Mariko Yoshida1#, Naoto Okubo1#, Naoyuki Chosa1, Tomokazu Hasegawa2, Miho Ibi1, Masaharu Kamo1, Seiko Kyakumoto1, Akira Ishisaki1✉

1. Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan
2. Department of Pediatric Dentistry, Tokushima University Hospital, Kuramoto-cho, Tokushima 770-8504, Japan
# These authors equally contributed to this work.

Citation:
Yoshida M, Okubo N, Chosa N, Hasegawa T, Ibi M, Kamo M, Kyakumoto S, Ishisaki A. TGF-β-Operated Growth Inhibition and Translineage Commitment into Smooth Muscle Cells of Periodontal Ligament-Derived Endothelial Progenitor Cells through Smad- and p38 MAPK-Dependent Signals. Int J Biol Sci 2012; 8(7):1062-1074. doi:10.7150/ijbs.4488. https://www.ijbs.com/v08p1062.htm
Other styles

File import instruction

Abstract

The periodontal ligament (PDL) is a fibrous connective tissue that attaches the tooth to the alveolar bone. We previously demonstrated the ability of PDL fibroblast-like cells to construct an endothelial cell (EC) marker-positive blood vessel-like structure, indicating the potential of fibroblastic lineage cells in PDL tissue as precursors of endothelial progenitor cells (EPCs) to facilitate the construction of a vascular system around damaged PDL tissue. A vascular regeneration around PDL tissue needs proliferation of vascular progenitor cells and the subsequent differentiation of the cells. Transforming growth factor-β (TGF-β) is known as an inducer of endothelial-mesenchymal transition (EndMT), however, it remains to be clarified what kinds of TGF-β signals affect growth and mesenchymal differentiation of PDL-derived EPC-like fibroblastic cells. Here, we demonstrated that TGF-β1 not only suppressed the proliferation of the PDL-derived EPC-like fibroblastic cells, but also induced smooth muscle cell (SMC) markers expression in the cells. On the other hand, TGF-β1 stimulation suppressed EC marker expression. Intriguingly, overexpression of Smad7, an inhibitor for TGF-β-induced Smad-dependent signaling, suppressed the TGF-β1-induced growth inhibition and SMC markers expression, but did not the TGF-β1-induced downregulation of EC marker expression. In contrast, p38 mitogen-activated protein kinase (MAPK) inhibitor SB 203580 suppressed the TGF-β1-induced downregulation of EC marker expression. In addition, the TGF-β1-induced SMC markers expression of the PDL-derived cells was reversed upon stimulation with fibroblast growth factor (FGF), suggesting that the TGF-β1 might not induce terminal SMC differentiation of the EPC-like fibroblastic cells. Thus, TGF-β1 not only negatively controls the growth of PDL-derived EPC-like fibroblastic cells via a Smad-dependent manner but also positively controls the SMC-differentiation of the cells possibly at the early stage of the translineage commitment via Smad- and p38 MAPK-dependent manners.

Keywords: Ligament, TGF-β, Differentiation, Endothelial Cell, Smooth Muscle Cell


Citation styles

APA
Yoshida, M., Okubo, N., Chosa, N., Hasegawa, T., Ibi, M., Kamo, M., Kyakumoto, S., Ishisaki, A. (2012). TGF-β-Operated Growth Inhibition and Translineage Commitment into Smooth Muscle Cells of Periodontal Ligament-Derived Endothelial Progenitor Cells through Smad- and p38 MAPK-Dependent Signals. International Journal of Biological Sciences, 8(7), 1062-1074. https://doi.org/10.7150/ijbs.4488.

ACS
Yoshida, M.; Okubo, N.; Chosa, N.; Hasegawa, T.; Ibi, M.; Kamo, M.; Kyakumoto, S.; Ishisaki, A. TGF-β-Operated Growth Inhibition and Translineage Commitment into Smooth Muscle Cells of Periodontal Ligament-Derived Endothelial Progenitor Cells through Smad- and p38 MAPK-Dependent Signals. Int. J. Biol. Sci. 2012, 8 (7), 1062-1074. DOI: 10.7150/ijbs.4488.

NLM
Yoshida M, Okubo N, Chosa N, Hasegawa T, Ibi M, Kamo M, Kyakumoto S, Ishisaki A. TGF-β-Operated Growth Inhibition and Translineage Commitment into Smooth Muscle Cells of Periodontal Ligament-Derived Endothelial Progenitor Cells through Smad- and p38 MAPK-Dependent Signals. Int J Biol Sci 2012; 8(7):1062-1074. doi:10.7150/ijbs.4488. https://www.ijbs.com/v08p1062.htm

CSE
Yoshida M, Okubo N, Chosa N, Hasegawa T, Ibi M, Kamo M, Kyakumoto S, Ishisaki A. 2012. TGF-β-Operated Growth Inhibition and Translineage Commitment into Smooth Muscle Cells of Periodontal Ligament-Derived Endothelial Progenitor Cells through Smad- and p38 MAPK-Dependent Signals. Int J Biol Sci. 8(7):1062-1074.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
Popup Image