Open Access

PDGF-induced PI3K-mediated signaling enhances the TGF‑β‑induced osteogenic differentiation of human mesenchymal stem cells in a TGF-β-activated MEK-dependent manner

  • Authors:
    • Jun Yokota
    • Naoyuki Chosa
    • Shunsuke Sawada
    • Naoto Okubo
    • Noriko Takahashi
    • Tomokazu Hasegawa
    • Hisatomo Kondo
    • Akira Ishisaki
  • View Affiliations

  • Published online on: December 27, 2013     https://doi.org/10.3892/ijmm.2013.1606
  • Pages: 534-542
  • Copyright: © Yokota et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Transforming growth factor-β (TGF-β) is a critical regulator of osteogenic differentiation and the platelet-derived growth factor (PDGF) is a chemoattractant or mitogen of osteogenic mesenchymal cells. However, the combined effects of these regulators on the osteogenic differentiation of mesenchymal cells remains unknown. In this study, we investigated the effects of TGF-β and/or PDGF on the osteogenic differentiation of human mesenchymal stem cells (hMSCs). The TGF-β-induced osteogenic differentiation of UE7T-13 cells, a bone marrow-derived hMSC line, was markedly enhanced by PDGF, although PDGF alone did not induce differentiation. TGF-β induced extracellular signal-regulated kinase (ERK) phosphorylation and PDGF induced Akt phosphorylation. In addition, the mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) inhibitor, U0126, suppressed the osteogenic differentiation induced by TGF-β alone. Moreover, U0126 completely suppressed the osteogenic differentiation synergistically induced by TGF-β and PDGF, whereas the phosphoinositide-3-kinase (PI3K) inhibitor, LY294002, only partially suppressed this effect. These results suggest that the enhancement of TGF-β-induced osteogenic differentiation by PDGF-induced PI3K/Akt-mediated signaling depends on TGF-β-induced MEK activity. Thus, PDGF positively modulates the TGF-β-induced osteogenic differentiation of hMSCs through synergistic crosstalk between MEK- and PI3K/Akt-mediated signaling.
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March 2014
Volume 33 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Yokota, J., Chosa, N., Sawada, S., Okubo, N., Takahashi, N., Hasegawa, T. ... Ishisaki, A. (2014). PDGF-induced PI3K-mediated signaling enhances the TGF‑β‑induced osteogenic differentiation of human mesenchymal stem cells in a TGF-β-activated MEK-dependent manner. International Journal of Molecular Medicine, 33, 534-542. https://doi.org/10.3892/ijmm.2013.1606
MLA
Yokota, J., Chosa, N., Sawada, S., Okubo, N., Takahashi, N., Hasegawa, T., Kondo, H., Ishisaki, A."PDGF-induced PI3K-mediated signaling enhances the TGF‑β‑induced osteogenic differentiation of human mesenchymal stem cells in a TGF-β-activated MEK-dependent manner". International Journal of Molecular Medicine 33.3 (2014): 534-542.
Chicago
Yokota, J., Chosa, N., Sawada, S., Okubo, N., Takahashi, N., Hasegawa, T., Kondo, H., Ishisaki, A."PDGF-induced PI3K-mediated signaling enhances the TGF‑β‑induced osteogenic differentiation of human mesenchymal stem cells in a TGF-β-activated MEK-dependent manner". International Journal of Molecular Medicine 33, no. 3 (2014): 534-542. https://doi.org/10.3892/ijmm.2013.1606