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

  1. Eiichi Hinoi1,2,6,
  2. Peter Bialek2,6,
  3. You-Tzung Chen3,
  4. Marie-Therese Rached2,
  5. Yoram Groner4,
  6. Richard R. Behringer3,
  7. David M. Ornitz5, and
  8. Gerard Karsenty1,2,7
  1. 1Department of Genetics and Development, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA;
  2. 2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA;
  3. 3Department of Molecular Genetics, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA;
  4. 4Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel;
  5. 5Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, USA

    1. ↵6 These authors contributed equally to this work.

    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.

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    1. Published in Advance October 18, 2006, doi: 10.1101/gad.1482906 Genes & Dev. 20: 2937-2942 Copyright © 2006, Cold Spring Harbor Laboratory Press

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