Hinoi Eiichi, Bialek Peter, Chen You-Tzung, Rached Marie-Therese, Groner Yoram, Behringer Richard R, Ornitz David M, Karsenty Gerard
Department of Genetics and Development, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Genes Dev. 2006 Nov 1;20(21):2937-42. doi: 10.1101/gad.1482906. Epub 2006 Oct 18.
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.
软骨膜是一种由围绕生长板软骨的未分化间充质细胞构成的结构，它通过尚未完全明确的机制调节软骨细胞的成熟。功能缺失和功能获得模型分析表明，Twist-1在软骨中的表达仅限于软骨膜，它以依赖Runx2的方式促进软骨细胞成熟。反过来，Runx2会增强Fgf18（一种软骨细胞成熟调节因子）在软骨膜中的表达。因此，Runx2和Fgf18缺失的复合杂合胚胎表现出与Fgf18基因敲除胚胎相同的软骨细胞成熟表型。本研究确定了软骨膜抑制软骨细胞成熟的转录基础，并揭示了Runx2在软骨形成过程中发挥着拮抗作用。
