Document Detail

WNT3A modulates chondrogenesis via canonical and non-canonical Wnt pathways in MSCs.
MedLine Citation:
PMID:  23276938     Owner:  NLM     Status:  MEDLINE    
The multilineage commitment of mesenchymal stem cells (MSCs) is controlled via unknown mechanisms. In this study, we investigated the regulation of the differentiation of MSCs into chondrocytes via the Wnt signaling pathway. Overexpression of WNT3A in MSCs activated both the canonical and non-canonical Wnt pathways, which were responsible for different WNT3A-induced outcomes. WNT3A promoted MSC proliferation via the ß-catenin-mediated canonical Wnt pathway, and inhibited chondrogenesis of MSCs via the calcium/calmodulin-dependent kinase II (CaMKII)-mediated non-canonical Wnt pathway. Interestingly, blockade of the canonical Wnt pathway by Dickkopf-related protein 1 exerted a synergistic effect on the inhibition of chondrogenesis of MSCs, while blockade of the non-canonical Wnt pathway by KN93 also exerted a synergistic effect on MSCs proliferation. These results suggest that the WNT3A-activated canonical and non-canonical pathways counteract each other in the setting of MSCs. This study provides evidence for the delicate regulation of the Wnt signaling cascade during chondrogenesis of MSCs, and suggests that genetic manipulation of the Wnt pathway may offer a powerful vehicle for modulating MSC differentiation in stem-cell-based cartilage repair.
Feng Qu; Junliang Wang; Ningru Xu; Chang Liu; Shuyuan Li; Ning Wang; Wei Qi; Haifeng Li; Chunbao Li; Zhenying Geng; Yujie Liu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-01
Journal Detail:
Title:  Frontiers in bioscience (Landmark edition)     Volume:  18     ISSN:  1093-4715     ISO Abbreviation:  Front Biosci (Landmark Ed)     Publication Date:  2013  
Date Detail:
Created Date:  2013-01-01     Completed Date:  2013-06-12     Revised Date:  2013-07-29    
Medline Journal Info:
Nlm Unique ID:  101612996     Medline TA:  Front Biosci (Landmark Ed)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  493-503     Citation Subset:  IM    
Department of orthopedics, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China.
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MeSH Terms
Cell Differentiation / drug effects
Chondrogenesis / drug effects*
Intercellular Signaling Peptides and Proteins / pharmacology
Mesenchymal Stromal Cells / drug effects,  metabolism*
Wnt Signaling Pathway / drug effects,  physiology*
Wnt3A Protein / physiology*
Reg. No./Substance:
0/DKK1 protein, human; 0/Intercellular Signaling Peptides and Proteins; 0/Wnt3A Protein

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