Runx2 inhibits chondrocyte proliferation and hypertrophy through its expression in the perichondrium.
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.
Hinoi
Eiichi
E
Department of Genetics and Development, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Bialek
Peter
P
Chen
You-Tzung
YT
Rached
Marie-Therese
MT
Groner
Yoram
Y
Behringer
Richard R
RR
Ornitz
David M
DM
Karsenty
Gerard
G
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology; D020219:Chondrogenesis / Q000235:genetics*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006132:Growth Plate / Q000196:embryology / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism
D050659:Core Binding Factor Alpha 1 Subunit; D009687:Nuclear Proteins; C493716:Runx2 protein, mouse; D051879:Twist-Related Protein 1; C113569:fibroblast growth factor 18; C067250:Twist1 protein, mouse; D005346:Fibroblast Growth Factors