Activation of non-canonical Wnt/JNK pathway by Wnt3a is associated with differentiation fate determination of human bone marrow stromal (mesenchymal) stem cells

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Resumé

The canonical Wnt signaling pathway can determine human bone marrow stromal (mesenchymal) stem cell (hMSC) differentiation fate into osteoblast or adipocyte lineages. However, its downstream targets in MSC are not well characterized. Thus, using DNA microarrays, we compared global gene expression patterns induced by Wnt3a treatment in two hMSC lines: hMSC-LRP5(T253) and hMSC-LRP5(T244) cells carrying known mutations of Wnt co-receptor LRP5 (T253I or T244M) that either enhances or represses canonical Wnt signaling, respectively. Wnt3a treatment of hMSC activated not only canonical Wnt signaling, but also the non-canonical Wnt/JNK pathway through upregulation of several non-canonical Wnt components e.g. naked cuticle 1 homolog (NKD1) and WNT11. Activation of the non-canonical Wnt/JNK pathway by anisomycin enhanced osteoblast differentiation whereas its inhibition by SP600125 enhanced adipocyte differentiation of hMSC. In conclusion, canonical and non-canonical Wnt signaling cooperate in determining MSC differentiation fate.
OriginalsprogEngelsk
TidsskriftBiochemical and Biophysical Research Communications
Vol/bind413
Udgave nummer1
Sider (fra-til)98-104
Antal sider7
ISSN0006-291X
DOI
StatusUdgivet - 16. sep. 2011

Fingeraftryk

Wnt Signaling Pathway
MAP Kinase Signaling System
Stem cells
Mesenchymal Stromal Cells
Bone
Chemical activation
Osteoblasts
Adipocytes
Wnt Receptors
Anisomycin
Microarrays
Gene expression
Cell Differentiation
Up-Regulation
Cell Line
Mutation
DNA

Citer dette

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title = "Activation of non-canonical Wnt/JNK pathway by Wnt3a is associated with differentiation fate determination of human bone marrow stromal (mesenchymal) stem cells",
abstract = "The canonical Wnt signaling pathway can determine human bone marrow stromal (mesenchymal) stem cell (hMSC) differentiation fate into osteoblast or adipocyte lineages. However, its downstream targets in MSC are not well characterized. Thus, using DNA microarrays, we compared global gene expression patterns induced by Wnt3a treatment in two hMSC lines: hMSC-LRP5(T253) and hMSC-LRP5(T244) cells carrying known mutations of Wnt co-receptor LRP5 (T253I or T244M) that either enhances or represses canonical Wnt signaling, respectively. Wnt3a treatment of hMSC activated not only canonical Wnt signaling, but also the non-canonical Wnt/JNK pathway through upregulation of several non-canonical Wnt components e.g. naked cuticle 1 homolog (NKD1) and WNT11. Activation of the non-canonical Wnt/JNK pathway by anisomycin enhanced osteoblast differentiation whereas its inhibition by SP600125 enhanced adipocyte differentiation of hMSC. In conclusion, canonical and non-canonical Wnt signaling cooperate in determining MSC differentiation fate.",
keywords = "Adipocytes, Anthracenes, Bone Marrow Cells, Carrier Proteins, Cell Differentiation, Cell Lineage, Cells, Cultured, Gene Expression Profiling, Humans, MAP Kinase Kinase 4, Mesenchymal Stem Cells, Osteoblasts, Protein Kinase Inhibitors, Signal Transduction, Stromal Cells, Wnt Proteins, Wnt3 Protein, Wnt3A Protein, beta Catenin",
author = "Weimin Qiu and Li Chen and Moustapha Kassem",
note = "Copyright {\circledC} 2011 Elsevier Inc. All rights reserved.",
year = "2011",
month = "9",
day = "16",
doi = "10.1016/j.bbrc.2011.08.061",
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TY - JOUR

T1 - Activation of non-canonical Wnt/JNK pathway by Wnt3a is associated with differentiation fate determination of human bone marrow stromal (mesenchymal) stem cells

AU - Qiu, Weimin

AU - Chen, Li

AU - Kassem, Moustapha

N1 - Copyright © 2011 Elsevier Inc. All rights reserved.

PY - 2011/9/16

Y1 - 2011/9/16

N2 - The canonical Wnt signaling pathway can determine human bone marrow stromal (mesenchymal) stem cell (hMSC) differentiation fate into osteoblast or adipocyte lineages. However, its downstream targets in MSC are not well characterized. Thus, using DNA microarrays, we compared global gene expression patterns induced by Wnt3a treatment in two hMSC lines: hMSC-LRP5(T253) and hMSC-LRP5(T244) cells carrying known mutations of Wnt co-receptor LRP5 (T253I or T244M) that either enhances or represses canonical Wnt signaling, respectively. Wnt3a treatment of hMSC activated not only canonical Wnt signaling, but also the non-canonical Wnt/JNK pathway through upregulation of several non-canonical Wnt components e.g. naked cuticle 1 homolog (NKD1) and WNT11. Activation of the non-canonical Wnt/JNK pathway by anisomycin enhanced osteoblast differentiation whereas its inhibition by SP600125 enhanced adipocyte differentiation of hMSC. In conclusion, canonical and non-canonical Wnt signaling cooperate in determining MSC differentiation fate.

AB - The canonical Wnt signaling pathway can determine human bone marrow stromal (mesenchymal) stem cell (hMSC) differentiation fate into osteoblast or adipocyte lineages. However, its downstream targets in MSC are not well characterized. Thus, using DNA microarrays, we compared global gene expression patterns induced by Wnt3a treatment in two hMSC lines: hMSC-LRP5(T253) and hMSC-LRP5(T244) cells carrying known mutations of Wnt co-receptor LRP5 (T253I or T244M) that either enhances or represses canonical Wnt signaling, respectively. Wnt3a treatment of hMSC activated not only canonical Wnt signaling, but also the non-canonical Wnt/JNK pathway through upregulation of several non-canonical Wnt components e.g. naked cuticle 1 homolog (NKD1) and WNT11. Activation of the non-canonical Wnt/JNK pathway by anisomycin enhanced osteoblast differentiation whereas its inhibition by SP600125 enhanced adipocyte differentiation of hMSC. In conclusion, canonical and non-canonical Wnt signaling cooperate in determining MSC differentiation fate.

KW - Adipocytes

KW - Anthracenes

KW - Bone Marrow Cells

KW - Carrier Proteins

KW - Cell Differentiation

KW - Cell Lineage

KW - Cells, Cultured

KW - Gene Expression Profiling

KW - Humans

KW - MAP Kinase Kinase 4

KW - Mesenchymal Stem Cells

KW - Osteoblasts

KW - Protein Kinase Inhibitors

KW - Signal Transduction

KW - Stromal Cells

KW - Wnt Proteins

KW - Wnt3 Protein

KW - Wnt3A Protein

KW - beta Catenin

U2 - 10.1016/j.bbrc.2011.08.061

DO - 10.1016/j.bbrc.2011.08.061

M3 - Journal article

C2 - 21875572

VL - 413

SP - 98

EP - 104

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 1

ER -