Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-9-17
pubmed:abstractText
The aberrant differentiation of pericytes along the adipogenic, chondrogenic, and osteogenic lineages may contribute to the development and progression of several vascular diseases, including atherosclerosis and calcific vasculopathies. However, the mechanisms controlling pericyte differentiation and, in particular, adipogenic and chondrogenic differentiation are poorly defined. Wnt/beta-catenin signaling regulates cell differentiation during embryonic and postnatal development, and there is increasing evidence that it is involved in vascular pathology. Therefore, this study tested the hypothesis that Wnt/beta-catenin signaling regulates the chondrogenic and adipogenic differentiation of pericytes. We demonstrate that pericytes express several Wnt receptors, including LDL receptor-related proteins 5 and 6, and Frizzled 1 to 4 and 7, 8, and 10, and that Wnt/beta-catenin signaling is stimulated by both Wnt3a and LiCl. Furthermore, induction of Wnt/beta-catenin signaling by LiCl enhances chondrogenesis in pericyte pellet cultures in the presence of transforming growth factor-beta3, as demonstrated by increased Sox-9 expression and glycosaminoglycan accumulation into the matrix. In contrast, transduction of pericytes with a recombinant adenovirus encoding dominant-negative T-cell factor-4 (RAd/dnTCF), which blocks Wnt/beta-catenin signaling, inhibited chondrogenesis, leading to reduced Sox-9 and type II collagen expression and less glycosaminoglycan accumulation. Together, these data demonstrate that transforming growth factor-beta3 induces the chondrogenic differentiation of pericytes by inducing Wnt/beta-catenin signaling and T-cell factor-induced gene transcription. Induction of Wnt/beta-catenin signaling also attenuates adipogenic differentiation of pericytes in both pellet and monolayer cultures, as demonstrated by decreased staining with oil red O and reduced peroxisome proliferator-activated receptor gamma2 expression. This effect was negated by transduction of pericytes with RAd/dnTCF. Together, these results demonstrate that Wnt/beta-catenin signaling inhibits adipogenic and enhances chondrogenic differentiation of pericytes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Aggrecans, http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type II, http://linkedlifedata.com/resource/pubmed/chemical/Frizzled Receptors, http://linkedlifedata.com/resource/pubmed/chemical/Glycosaminoglycans, http://linkedlifedata.com/resource/pubmed/chemical/High Mobility Group Proteins, http://linkedlifedata.com/resource/pubmed/chemical/LDL-Receptor Related Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Lithium Chloride, http://linkedlifedata.com/resource/pubmed/chemical/Proteoglycans, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/SOX9 Transcription Factor, http://linkedlifedata.com/resource/pubmed/chemical/TCF Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta3, http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Wnt3 Protein, http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
14
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
581-9
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:17673669-Adipogenesis, pubmed-meshheading:17673669-Aggrecans, pubmed-meshheading:17673669-Animals, pubmed-meshheading:17673669-Cattle, pubmed-meshheading:17673669-Cells, Cultured, pubmed-meshheading:17673669-Chondrogenesis, pubmed-meshheading:17673669-Collagen Type II, pubmed-meshheading:17673669-Frizzled Receptors, pubmed-meshheading:17673669-Glycosaminoglycans, pubmed-meshheading:17673669-High Mobility Group Proteins, pubmed-meshheading:17673669-LDL-Receptor Related Proteins, pubmed-meshheading:17673669-Lipid Metabolism, pubmed-meshheading:17673669-Lithium Chloride, pubmed-meshheading:17673669-Pericytes, pubmed-meshheading:17673669-Proteoglycans, pubmed-meshheading:17673669-RNA, Messenger, pubmed-meshheading:17673669-SOX9 Transcription Factor, pubmed-meshheading:17673669-Signal Transduction, pubmed-meshheading:17673669-TCF Transcription Factors, pubmed-meshheading:17673669-Transcription, Genetic, pubmed-meshheading:17673669-Transcription Factors, pubmed-meshheading:17673669-Transduction, Genetic, pubmed-meshheading:17673669-Transforming Growth Factor beta3, pubmed-meshheading:17673669-Vascular Diseases, pubmed-meshheading:17673669-Wnt Proteins, pubmed-meshheading:17673669-Wnt3 Protein, pubmed-meshheading:17673669-beta Catenin
pubmed:year
2007
pubmed:articleTitle
Wnt/beta-catenin signaling stimulates chondrogenic and inhibits adipogenic differentiation of pericytes: potential relevance to vascular disease?
pubmed:affiliation
UK Centre for Tissue Engineering, University of Manchester, Manchester M13 9PT, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't