Running Against the Wnt: How Wnt/β-Catenin Suppresses Adipogenesis

Mesenchymal stem cells (MSCs) give rise to adipocytes, osteocytes, and chondrocytes and reside in various tissues, including bone marrow and adipose tissue. The differentiation choices of MSCs are controlled by several signaling pathways, including the Wnt/β-catenin signaling. When MSCs undergo adip...

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Main Authors: Twan J. J. de Winter, Roeland Nusse
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-02-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2021.627429/full
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author Twan J. J. de Winter
Roeland Nusse
Roeland Nusse
author_facet Twan J. J. de Winter
Roeland Nusse
Roeland Nusse
author_sort Twan J. J. de Winter
collection DOAJ
description Mesenchymal stem cells (MSCs) give rise to adipocytes, osteocytes, and chondrocytes and reside in various tissues, including bone marrow and adipose tissue. The differentiation choices of MSCs are controlled by several signaling pathways, including the Wnt/β-catenin signaling. When MSCs undergo adipogenesis, they first differentiate into preadipocytes, a proliferative adipocyte precursor cell, after which they undergo terminal differentiation into mature adipocytes. These two steps are controlled by the Wnt/β-catenin pathway, in such a way that when signaling is abrogated, the next step in adipocyte differentiation can start. This sequence suggests that the main role of Wnt/β-catenin signaling is to suppress differentiation while increasing MSC and preadipocytes cell mass. During later steps of MSC differentiation, however, active Wnt signaling can promote osteogenesis instead of keeping the MSCs undifferentiated and proliferative. The exact mechanisms behind the various functions of Wnt signaling remain elusive, although recent research has revealed that during lineage commitment of MSCs into preadipocytes, Wnt signaling is inactivated by endogenous Wnt inhibitors. In part, this process is regulated by histone-modifying enzymes, which can lead to increased or decreased Wnt gene expression. The role of Wnt in adipogenesis, as well as in osteogenesis, has implications for metabolic diseases since Wnt signaling may serve as a therapeutic target.
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spelling doaj.art-05ee81d822db4073b266ad6d04c952b82022-12-21T23:15:35ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-02-01910.3389/fcell.2021.627429627429Running Against the Wnt: How Wnt/β-Catenin Suppresses AdipogenesisTwan J. J. de Winter0Roeland Nusse1Roeland Nusse2Faculty of Medicine, University Medical Centre Utrecht, Utrecht, NetherlandsDepartment of Developmental Biology, Howard Hughes Medical Institute, Stanford, CA, United StatesSchool of Medicine, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, United StatesMesenchymal stem cells (MSCs) give rise to adipocytes, osteocytes, and chondrocytes and reside in various tissues, including bone marrow and adipose tissue. The differentiation choices of MSCs are controlled by several signaling pathways, including the Wnt/β-catenin signaling. When MSCs undergo adipogenesis, they first differentiate into preadipocytes, a proliferative adipocyte precursor cell, after which they undergo terminal differentiation into mature adipocytes. These two steps are controlled by the Wnt/β-catenin pathway, in such a way that when signaling is abrogated, the next step in adipocyte differentiation can start. This sequence suggests that the main role of Wnt/β-catenin signaling is to suppress differentiation while increasing MSC and preadipocytes cell mass. During later steps of MSC differentiation, however, active Wnt signaling can promote osteogenesis instead of keeping the MSCs undifferentiated and proliferative. The exact mechanisms behind the various functions of Wnt signaling remain elusive, although recent research has revealed that during lineage commitment of MSCs into preadipocytes, Wnt signaling is inactivated by endogenous Wnt inhibitors. In part, this process is regulated by histone-modifying enzymes, which can lead to increased or decreased Wnt gene expression. The role of Wnt in adipogenesis, as well as in osteogenesis, has implications for metabolic diseases since Wnt signaling may serve as a therapeutic target.https://www.frontiersin.org/articles/10.3389/fcell.2021.627429/fulladipogenesisWnt signalingmesenchymal stem cellspreadipocyteosteogenesisC/EBP
spellingShingle Twan J. J. de Winter
Roeland Nusse
Roeland Nusse
Running Against the Wnt: How Wnt/β-Catenin Suppresses Adipogenesis
Frontiers in Cell and Developmental Biology
adipogenesis
Wnt signaling
mesenchymal stem cells
preadipocyte
osteogenesis
C/EBP
title Running Against the Wnt: How Wnt/β-Catenin Suppresses Adipogenesis
title_full Running Against the Wnt: How Wnt/β-Catenin Suppresses Adipogenesis
title_fullStr Running Against the Wnt: How Wnt/β-Catenin Suppresses Adipogenesis
title_full_unstemmed Running Against the Wnt: How Wnt/β-Catenin Suppresses Adipogenesis
title_short Running Against the Wnt: How Wnt/β-Catenin Suppresses Adipogenesis
title_sort running against the wnt how wnt β catenin suppresses adipogenesis
topic adipogenesis
Wnt signaling
mesenchymal stem cells
preadipocyte
osteogenesis
C/EBP
url https://www.frontiersin.org/articles/10.3389/fcell.2021.627429/full
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