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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2006-11-8
pubmed:abstractText
Bone morphogenetic protein (BMP) signaling pathways are essential regulators of chondrogenesis. However, the roles of these pathways in vivo are not well understood. Limb-culture studies have provided a number of essential insights, including the demonstration that BMP pathways are required for chondrocyte proliferation and differentiation. However, limb-culture studies have yielded contradictory results; some studies indicate that BMPs exert stimulatory effects on differentiation, whereas others support inhibitory effects. Therefore, we characterized the skeletal phenotypes of mice lacking Bmpr1a in chondrocytes (Bmpr1a(CKO)) and Bmpr1a(CKO);Bmpr1b+/- (Bmpr1a(CKO);1b+/-) in order to test the roles of BMP pathways in the growth plate in vivo. These mice reveal requirements for BMP signaling in multiple aspects of chondrogenesis. They also demonstrate that the balance between signaling outputs from BMP and fibroblast growth factor (FGF) pathways plays a crucial role in the growth plate. These studies indicate that BMP signaling is required to promote Ihh expression, and to inhibit activation of STAT and ERK1/2 MAPK, key effectors of FGF signaling. BMP pathways inhibit FGF signaling, at least in part, by inhibiting the expression of FGFR1. These results provide a genetic in vivo demonstration that the progression of chondrocytes through the growth plate is controlled by antagonistic BMP and FGF signaling pathways.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
133
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4667-78
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17065231-Animals, pubmed-meshheading:17065231-Apoptosis, pubmed-meshheading:17065231-Bone Morphogenetic Protein Receptors, Type I, pubmed-meshheading:17065231-Bone Morphogenetic Proteins, pubmed-meshheading:17065231-Cell Proliferation, pubmed-meshheading:17065231-Chondrogenesis, pubmed-meshheading:17065231-Female, pubmed-meshheading:17065231-Fibroblast Growth Factors, pubmed-meshheading:17065231-Growth Plate, pubmed-meshheading:17065231-Hedgehog Proteins, pubmed-meshheading:17065231-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:17065231-Male, pubmed-meshheading:17065231-Mice, pubmed-meshheading:17065231-Mice, Knockout, pubmed-meshheading:17065231-Mice, Mutant Strains, pubmed-meshheading:17065231-Mutation, pubmed-meshheading:17065231-Osteochondrodysplasias, pubmed-meshheading:17065231-Phenotype, pubmed-meshheading:17065231-Receptor, Fibroblast Growth Factor, Type 1, pubmed-meshheading:17065231-Signal Transduction
pubmed:year
2006
pubmed:articleTitle
BMPs regulate multiple aspects of growth-plate chondrogenesis through opposing actions on FGF pathways.
pubmed:affiliation
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
pubmed:publicationType
Journal Article