Open Access

Notch signaling pathway promotes osteogenic differentiation of mesenchymal stem cells by enhancing BMP9/Smad signaling

  • Authors:
    • Junjie Cao
    • Yalin Wei
    • Jing Lian
    • Lunyun Yang
    • Xiaoyan Zhang
    • Jiaying Xie
    • Qiang Liu
    • Jinyong Luo
    • Baicheng He
    • Min Tang
  • View Affiliations

  • Published online on: June 22, 2017     https://doi.org/10.3892/ijmm.2017.3037
  • Pages:378-388
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Abstract

Notch is an important pathway in that it regulates cell-to-cell signal transduction, which plays an essential role in skeletal remodeling. Bone morphogenetic protein (BMP)9 has been regarded as one of the most efficient BMPs by which to induce osteogenic differentiation in mesenchymal stem cells (MSCs). Understanding the interaction between Notch and BMP9 signaling is a critical issue for optimizing the application of MSCs and BMPs in bone tissue engineering. In the present study, we investigated the role of Notch signaling in the BMP9‑induced osteogenic differentiation of MSCs. Our data demonstrated that Notch signaling obviously enhanced BMP9‑induced osteogenic differentiation in MSCs in vitro and in vivo. Notch signaling augmented the activity of BMP9‑induced BMP/Smad signaling and increased the gene expression of essential osteogenic factors induced by BMP9 in MSCs, such as runt‑related transcription factor 2 (Runx2), type I collagen (Colla1) and inhibitor of differentiation (Id)1. We also found that Notch signaling promoted the expression of activin‑like kinase 2 (ALK2) induced by BMP9, and the inhibitory effect of dnALK2 on BMP9‑induced osteogenic differentiation was rescued by constitutive overexpression of Delta‑like 1 (DLL1). Notch signaling also exhibited an apparent effect on the proliferation of mouse embryo fibroblasts (MEFs) during BMP9‑induced osteogenic differentiation. These results indicate that Notch plays a significant role in mediating BMP9‑induced osteogenic differentiation in MSCs, which may be partly regulated by upregulation of the expression of ALK2.

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August 2017
Volume 40 Issue 2

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

2016 Impact Factor: 2.341
Ranked #21/128 Medicine Research and Experimental
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APA
Cao, J., Wei, Y., Lian, J., Yang, L., Zhang, X., Xie, J. ... Tang, M. (2017). Notch signaling pathway promotes osteogenic differentiation of mesenchymal stem cells by enhancing BMP9/Smad signaling. International Journal of Molecular Medicine, 40, 378-388. https://doi.org/10.3892/ijmm.2017.3037
MLA
Cao, J., Wei, Y., Lian, J., Yang, L., Zhang, X., Xie, J., Liu, Q., Luo, J., He, B., Tang, M."Notch signaling pathway promotes osteogenic differentiation of mesenchymal stem cells by enhancing BMP9/Smad signaling". International Journal of Molecular Medicine 40.2 (2017): 378-388.
Chicago
Cao, J., Wei, Y., Lian, J., Yang, L., Zhang, X., Xie, J., Liu, Q., Luo, J., He, B., Tang, M."Notch signaling pathway promotes osteogenic differentiation of mesenchymal stem cells by enhancing BMP9/Smad signaling". International Journal of Molecular Medicine 40, no. 2 (2017): 378-388. https://doi.org/10.3892/ijmm.2017.3037