IGFBP2 enhances adipogenic differentiation potentials of mesenchymal stem cells from Wharton's jelly of the umbilical cord via JNK and Akt signaling pathways.

Mesenchymal stem cell (MSC)-mediated tissue engineering represents a promising strategy to address adipose tissue defects. MSCs derived from Wharton's jelly of the umbilical cord (WJCMSCs) may serve as an ideal source for adipose tissue engineering due to their abundance, safety profile, and ac...

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Main Authors: Yuejun Wang, Yunsong Liu, Zhipeng Fan, Dayong Liu, Fu Wang, Yongsheng Zhou
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0184182&type=printable
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author Yuejun Wang
Yunsong Liu
Zhipeng Fan
Dayong Liu
Fu Wang
Yongsheng Zhou
author_facet Yuejun Wang
Yunsong Liu
Zhipeng Fan
Dayong Liu
Fu Wang
Yongsheng Zhou
author_sort Yuejun Wang
collection DOAJ
description Mesenchymal stem cell (MSC)-mediated tissue engineering represents a promising strategy to address adipose tissue defects. MSCs derived from Wharton's jelly of the umbilical cord (WJCMSCs) may serve as an ideal source for adipose tissue engineering due to their abundance, safety profile, and accessibility. How to activate the directed differentiation potentials of WJCMSCs is the core point for their clinical applications. A thorough investigation of mechanisms involved in WJCMSC adipogenic differentiation is necessary to support their application in adipose tissue engineering and address shortcomings. Previous study showed, compared with periodontal ligament stem cells (PDLSCs), WJCMSCs had a weakened adipogenic differentiation potentials and lower expression of insulin-like growth factor binding protein 2 (IGFBP2). IGFBP2 may be involved in the adipogenesis of MSCs. Generally, IGFBP2 is involved in regulating biological activity of insulin-like growth factors, however, its functions in human MSCs are unclear. Here, we found IGFBP2 expression was upregulated upon adipogenic induction, and that IGFBP2 enhanced adipogenic differentiation of WJCMSCs and BMSCs. Moreover, IGFBP2 increased phosphorylation of c-Jun N-terminal kinase (p-JNK) and p-Akt, and activated JNK or Akt signaling significantly promoted adipogenic differentiation of MSCs. Furthermore, inhibitor-mediated blockage of either JNK or Akt signaling dramatically reduced IGFBP2-mediated adipogenic differentiation. And the JNK inhibitor, SP600125 markedly blocked IGFBP2-mediated Akt activation. Moreover, IGFBP2 was negatively regulated by BCOR, which inhibited adipogenic differentiation of WJCMSCs. Overall, our results reveal a new function of IGFBP2, providing a novel insight into the mechanism of adipogenic differentiation and identifying a potential target mediator for improving adipose tissue engineering based on WJCMSCs.
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spelling doaj-art-797e8b1069804f65b52ac509e8b8edca2025-08-20T02:45:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01128e018418210.1371/journal.pone.0184182IGFBP2 enhances adipogenic differentiation potentials of mesenchymal stem cells from Wharton's jelly of the umbilical cord via JNK and Akt signaling pathways.Yuejun WangYunsong LiuZhipeng FanDayong LiuFu WangYongsheng ZhouMesenchymal stem cell (MSC)-mediated tissue engineering represents a promising strategy to address adipose tissue defects. MSCs derived from Wharton's jelly of the umbilical cord (WJCMSCs) may serve as an ideal source for adipose tissue engineering due to their abundance, safety profile, and accessibility. How to activate the directed differentiation potentials of WJCMSCs is the core point for their clinical applications. A thorough investigation of mechanisms involved in WJCMSC adipogenic differentiation is necessary to support their application in adipose tissue engineering and address shortcomings. Previous study showed, compared with periodontal ligament stem cells (PDLSCs), WJCMSCs had a weakened adipogenic differentiation potentials and lower expression of insulin-like growth factor binding protein 2 (IGFBP2). IGFBP2 may be involved in the adipogenesis of MSCs. Generally, IGFBP2 is involved in regulating biological activity of insulin-like growth factors, however, its functions in human MSCs are unclear. Here, we found IGFBP2 expression was upregulated upon adipogenic induction, and that IGFBP2 enhanced adipogenic differentiation of WJCMSCs and BMSCs. Moreover, IGFBP2 increased phosphorylation of c-Jun N-terminal kinase (p-JNK) and p-Akt, and activated JNK or Akt signaling significantly promoted adipogenic differentiation of MSCs. Furthermore, inhibitor-mediated blockage of either JNK or Akt signaling dramatically reduced IGFBP2-mediated adipogenic differentiation. And the JNK inhibitor, SP600125 markedly blocked IGFBP2-mediated Akt activation. Moreover, IGFBP2 was negatively regulated by BCOR, which inhibited adipogenic differentiation of WJCMSCs. Overall, our results reveal a new function of IGFBP2, providing a novel insight into the mechanism of adipogenic differentiation and identifying a potential target mediator for improving adipose tissue engineering based on WJCMSCs.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0184182&type=printable
spellingShingle Yuejun Wang
Yunsong Liu
Zhipeng Fan
Dayong Liu
Fu Wang
Yongsheng Zhou
IGFBP2 enhances adipogenic differentiation potentials of mesenchymal stem cells from Wharton's jelly of the umbilical cord via JNK and Akt signaling pathways.
PLoS ONE
title IGFBP2 enhances adipogenic differentiation potentials of mesenchymal stem cells from Wharton's jelly of the umbilical cord via JNK and Akt signaling pathways.
title_full IGFBP2 enhances adipogenic differentiation potentials of mesenchymal stem cells from Wharton's jelly of the umbilical cord via JNK and Akt signaling pathways.
title_fullStr IGFBP2 enhances adipogenic differentiation potentials of mesenchymal stem cells from Wharton's jelly of the umbilical cord via JNK and Akt signaling pathways.
title_full_unstemmed IGFBP2 enhances adipogenic differentiation potentials of mesenchymal stem cells from Wharton's jelly of the umbilical cord via JNK and Akt signaling pathways.
title_short IGFBP2 enhances adipogenic differentiation potentials of mesenchymal stem cells from Wharton's jelly of the umbilical cord via JNK and Akt signaling pathways.
title_sort igfbp2 enhances adipogenic differentiation potentials of mesenchymal stem cells from wharton s jelly of the umbilical cord via jnk and akt signaling pathways
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0184182&type=printable
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