Abstract
The perichondrium, a structure made of undifferentiated mesenchymal cells surrounding growth plate cartilage, regulates chondrocyte maturation through poorly understood mechanisms. Analyses of loss- and gain-of-function models show that Twist-1, whose expression in cartilage is restricted to perichondrium, favors chondrocyte maturation in a Runx2-dependent manner. Runx2, in turn, enhances perichondrial expression of Fgf18, a regulator of chondrocyte maturation. Accordingly, compound heterozygous embryos for Runx2 and Fgf18 deletion display the same chondrocyte maturation phenotype as Fgf18-null embryos. This study identifies a transcriptional basis for the inhibition of chondrocyte maturation by perichondrium and reveals that Runx2 fulfills antagonistic functions during chondrogenesis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation
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Cell Proliferation
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Chondrocytes / cytology
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Chondrocytes / physiology
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Chondrogenesis / genetics*
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Core Binding Factor Alpha 1 Subunit / genetics
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Core Binding Factor Alpha 1 Subunit / physiology*
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Fibroblast Growth Factors / genetics*
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Fibroblast Growth Factors / metabolism
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Gene Deletion
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Gene Expression Regulation, Developmental*
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Growth Plate / embryology
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Growth Plate / metabolism
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Mesoderm / cytology
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Mesoderm / metabolism*
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Mice
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Mice, Mutant Strains
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Twist-Related Protein 1 / genetics
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Twist-Related Protein 1 / metabolism
Substances
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Core Binding Factor Alpha 1 Subunit
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Nuclear Proteins
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Runx2 protein, mouse
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Twist-Related Protein 1
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fibroblast growth factor 18
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Twist1 protein, mouse
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Fibroblast Growth Factors