Abstract
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.
Highlights
Decades of research has established a main role of Wnt signaling in stem cell fate and control (Nusse, 2008; Van Camp et al, 2014)
Wnt signaling impacts the expression of key transcription factors important in adipocyte differentiation, as has been shown by the MacDougald lab: active Wnt signaling in preadipocytes lowers RNA and protein levels of transcription factors C/EBPα and Peroxisome proliferator-activated receptor γ (PPARγ), both needed for terminal differentiation
Inhibition of Lysyl oxidase (Lox) results in an absence of adipogenesis and leads to an elevated activation of the Wnt signaling pathway and BMP4induced osteogenesis (Jiang et al, 2018). These findings suggest that the on or off state of the canonical Wnt pathway determines the lineage potential during BMP-induced differentiation of Mesenchymal stem cells (MSCs)
Summary
Decades of research has established a main role of Wnt signaling in stem cell fate and control (Nusse, 2008; Van Camp et al, 2014). Wnt signaling is involved in differentiation and lineage fate decisions, as evinced in embryonic hematopoietic stem cell development (Richter et al, 2017). In mesenchymal stem cell (MSC) biology, activation of the β-catenin-dependent canonical Wnt pathway is essential to induce osteogenic differentiation (Kang et al, 2007). It has become clear that Wnt signaling plays a major role in the process of adipogenesis, the differentiation of MSCs into mature fat cells, or adipocytes. How Wnt/β-Catenin Suppresses Adipogenesis involved during the first stages of adipogenesis, when adipocyte commitment is at the expense of osteogenesis, the formation of bone cells (Han et al, 2019). We aim at clarifying the role of Wnt signaling from MSCs until adipogenesis
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