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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.

Runx2 inhibits chondrocyte proliferation and hypertrophy through its expression in the perichondrium