title: WNT3A modulates chondrogenesis via canonical and non-canonical Wnt pathways in MSCs.
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 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.
authors.affiliation: Department of orthopedics, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qu
authors.forename: Junliang
authors.initials: J
authors.lastname: Wang
authors.forename: Ningru
authors.initials: N
authors.lastname: Xu
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Qi
authors.forename: Haifeng
authors.initials: H
authors.lastname: Li
authors.forename: Chunbao
authors.initials: C
authors.lastname: Li
authors.forename: Zhenying
authors.initials: Z
authors.lastname: Geng
authors.forename: Yujie
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology*; D060509:Wnt3A Protein / Q000502:physiology*
chemical_list: C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D060509:Wnt3A Protein