title: Inactivation of Wnt/β-catenin signaling in human adipose-derived stem cells is necessary for chondrogenic differentiation and maintenance.
abstract: The Wnt/β-catenin signaling pathway plays critical roles in self-renewal and differentiation of mesenchymal stem cells. However, very little is known about its role in the chondrogenesis of human adipose-derived stem cells (hADSCs). In this study, we analyzed protein expression of several key components of the Wnt/β-catenin signaling pathway using a 21-day in vitro model of hADSC chondrogenesis. Wnt1, β-catenin, and GSK3β levels increased sharply at day 12, peaked at day 18, and then declined. Expression of TCF1, a target gene of Wnt/β-catenin signaling, closely followed that of Wnt1. These results were consistent with changes in endonuclear β-catenin levels. Gene expression of the chondrocyte-specific markers, collagen type II (COL II), SOX9, and aggrecan, increased during hADSC chondrogenesis, peaked at day 12, and then declined. Adding a Wnt inhibitor (days 0-21) resulted in consistently elevated levels of COL II, SOX9, and aggrecan mRNA. In contrast, adding Wnt1 (days 0-21) to cultures led to sustained Wnt/β-catenin signaling over the 21 days and suppressed expression of chondrocyte-specific markers. Moreover, adding Wnt1 at late stages of differentiation (day 18) further diminished chondrocyte-specific marker expression. Together, these results showed that inactivation of Wnt/β-catenin signaling is needed for the progression of chondrogenesis and the maturation and phenotype maintenance of chondroid cells.
authors.affiliation: The First Affiliated Hospital, Jinan University, Guangzhou 510632, China; Institute of Orthopaedic Disease Research, Jinan University, Guangzhou 510632, China. Electronic address: luosimin728@jnu.edu.cn.
authors.forename: Simin
authors.initials: S
authors.lastname: Luo
authors.forename: Qiping
authors.initials: Q
authors.lastname: Shi
authors.forename: Zhengang
authors.initials: Z
authors.lastname: Zha
authors.forename: Ping
authors.initials: P
authors.lastname: Yao
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Lin
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Shangyun
authors.initials: S
authors.lastname: Sun
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology*; D020219:Chondrogenesis / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D008024:Ligands; D018613:Microscopy, Confocal; D060888:Real-Time Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology*; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D008024:Ligands; D051153:Wnt Proteins; D051176:beta Catenin
keywords: Chondroid cells; Dedifferentiation; HADSCs; Wnt/β-catenin signaling