Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2006-8-28
pubmed:abstractText
Both the Wnt/beta-catenin and Ihh signaling pathways play essential roles in crucial aspects of endochondral ossification: osteoblast differentiation, chondrocyte proliferation and hypertrophy. To understand the genetic interaction between these two signaling pathways, we have inactivated the beta-catenin gene and upregulated Ihh signaling simultaneously in the same cells during endochondral skeletal development using beta-catenin and patched 1 floxed alleles. We uncovered previously unexpected roles of Ihh signaling in synovial joint formation and the essential function of Wnt/beta-catenin signaling in regulating chondrocyte survival. More importantly, we found that Wnt and Ihh signaling interact with each other in distinct ways to control osteoblast differentiation, chondrocyte proliferation, hypertrophy, survival and synovial joint formation in the developing endochondral bone. Beta-catenin is required downstream of Ihh signaling and osterix expression for osteoblast differentiation. But in chondrocyte survival, beta-catenin is required upstream of Ihh signaling to inhibit chondrocyte apoptosis. In addition, Ihh signaling can inhibit chondrocyte hypertrophy and synovial joint formation independently of beta-catenin. However, there is a strong synergistic interaction between Wnt/beta-catenin and Ihh signaling in regulating synovial joint formation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
133
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3695-707
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16936073-Animals, pubmed-meshheading:16936073-Apoptosis, pubmed-meshheading:16936073-Bone and Bones, pubmed-meshheading:16936073-Cartilage, pubmed-meshheading:16936073-Cell Cycle, pubmed-meshheading:16936073-Cell Differentiation, pubmed-meshheading:16936073-Cell Proliferation, pubmed-meshheading:16936073-Cell Survival, pubmed-meshheading:16936073-Chondrocytes, pubmed-meshheading:16936073-Gene Expression Regulation, Developmental, pubmed-meshheading:16936073-Hedgehog Proteins, pubmed-meshheading:16936073-Immunohistochemistry, pubmed-meshheading:16936073-In Situ Hybridization, pubmed-meshheading:16936073-In Situ Nick-End Labeling, pubmed-meshheading:16936073-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:16936073-Joints, pubmed-meshheading:16936073-Mice, pubmed-meshheading:16936073-Osteoblasts, pubmed-meshheading:16936073-Osteogenesis, pubmed-meshheading:16936073-Receptors, Cell Surface, pubmed-meshheading:16936073-Signal Transduction, pubmed-meshheading:16936073-Wnt Proteins, pubmed-meshheading:16936073-beta Catenin
pubmed:year
2006
pubmed:articleTitle
Wnt/beta-catenin signaling interacts differentially with Ihh signaling in controlling endochondral bone and synovial joint formation.
pubmed:affiliation
Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural