Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-3-17
pubmed:abstractText
Although genetic evidence has demonstrated a role for Wnt5b during cartilage and limb development, little is known about the mechanisms underlying Wnt5b-regulated chondrocyte differentiation. We observed that Wnt5b inhibited chondrocyte hypertrophy and expression of type X collagen. In addition, Wnt5b regulated the overall size of chondrogenic cultures, suggesting that Wnt5b regulates other processes involved in cartilage development. We therefore investigated the signaling pathways by which Wnt5b influences differentiation. Wnt5b activated known calcium-dependent signaling pathways and JNK, a component of the planar cell polarity pathway. Since the planar cell polarity pathway regulates process such as cell migration and cell aggregation that are involved in limb development, we assayed for effects of Wnt5b on these processes. We observed a marked increase chondroprogenitor cell migration with Wnt5b expression. This effect was blocked by inhibition of JNK, but not by inhibition of other Wnt5b-responsive factors. Expression of Wnt5b also disrupted the cellular aggregation associated with mesenchymal condensation. Decreased aggregation was associated with reduced cadherin expression as well as increased cadherin receptor turnover. This increase in cadherin receptor turnover was associated with an increase in Src-dependent beta-catenin phosphorylation downstream of Wnt5b. Our data demonstrate that not only does Wnt5b inhibit chondrocyte hypertrophy, but document a novel role for Wnt5b in modulating cellular migration through the JNK-dependent and cell adhesion through an activation of Src and subsequent cadherin receptor turnover.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1097-4652
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
226
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1683-93
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Wnt5b regulates mesenchymal cell aggregation and chondrocyte differentiation through the planar cell polarity pathway.
pubmed:affiliation
Department of Orthopeadic Surgery, University of Connecticut Health Center, Farmington, Connecticut 06062, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't