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Int. J. Mol. Sci. 2015, 16(9), 20344-20359; doi:10.3390/ijms160920344

BMP3 Alone and Together with TGF-β Promote the Differentiation of Human Mesenchymal Stem Cells into a Nucleus Pulposus-Like Phenotype

Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, 310009 Hangzhou, China
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Academic Editor: Wilhelm Bloch
Received: 26 July 2015 / Revised: 15 August 2015 / Accepted: 21 August 2015 / Published: 27 August 2015
(This article belongs to the Special Issue Stem Cell Activation in Adult Organism)
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Abstract

Human mesenchymal stem cells (MSCs) have the potential to differentiate into nucleus pulposus (NP)-like cells under specific stimulatory conditions. Thus far, the effects of bone morphogenetic protein 3 (BMP3) and the cocktail effects of BMP3 and transforming growth factor (TGF)-β on MSC proliferation and differentiation remain obscure. Therefore, this study was designed to clarify these unknowns. MSCs were cultured with various gradients of BMP3 and BMP3/TGF-β, and compared with cultures in basal and TGF-β media. Cell proliferation, glycosaminoglycan (GAG) content, gene expression, and signaling proteins were measured to assess the effects of BMP3 and BMP3/TGF-β on MSCs. Cell number and GAG content increased upon the addition of BMP3 in a dose-dependent manner. The expression of COL2A1, ACAN, SOX9, and KRT19 increased following induction with BMP3 and TGF-β, in contrast to that of COL1A1, ALP, OPN, and COMP. Smad3 phosphorylation was upregulated by BMP3 and TGF-β, but BMP3 did not affect the phosphorylation of extracellular-signal regulated kinase (ERK) 1/2 or c-Jun N-terminal kinase (JNK). Our results reveal that BMP3 enhances MSC proliferation and differentiation into NP-like cells, as indicated by increased cell numbers and specific gene expressions, and may also cooperate with TGF-β induced positive effects. These actions are likely related to the activation of TGF-β signaling pathway. View Full-Text
Keywords: differentiation; mesenchymal stem cells; transforming growth factor-β; bone morphogenetic protein-3; nucleus pulposus-like cells differentiation; mesenchymal stem cells; transforming growth factor-β; bone morphogenetic protein-3; nucleus pulposus-like cells
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Zhou, X.; Tao, Y.; Liang, C.; Zhang, Y.; Li, H.; Chen, Q. BMP3 Alone and Together with TGF-β Promote the Differentiation of Human Mesenchymal Stem Cells into a Nucleus Pulposus-Like Phenotype. Int. J. Mol. Sci. 2015, 16, 20344-20359.

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