IMR Press / FBL / Volume 18 / Issue 2 / DOI: 10.2741/4116

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
WNT3A modulates chondrogenesis via canonical and non-canonical Wnt pathways in MSCs
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1 Medical school of Nankai University, 94 Weijin Road, Tianjin, China
2 Department of orthopedics, Chinese PLA general hospital, 28 Fuxing Road, Beijing, China
Academic Editor:Jie Zou
Front. Biosci. (Landmark Ed) 2013, 18(2), 493–503; https://doi.org/10.2741/4116
Published: 1 January 2013
(This article belongs to the Special Issue Immunoregulation and inflammatory disease)
Abstract

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 WNT3Ainduced outcomes. WNT3A promoted MSC proliferation via the β-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 Dickkopfrelated 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.

Keywords
Wnt3A; Mesenchymal
Stem Cells
Induced
Pluripotent
Adult
Human
Articular
Chondrocytes
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