Nkx3.2/Bapx1 acts as a negative regulator of chondrocyte maturation

Sylvain Provot, Hervé Kempf, L. Charles Murtaugh, Ung Il Chung, Dae Won Kim, Jay Chyung, Henry M. Kronenberg, Andrew B. Lassar

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Parathyroid hormone-related protein (PTHrP) is essential to maintain a pool of dividing, immature chondrocytes in the growth plate of long bones. In chick and mouse, expression of Nkx3.2/Bapx1 in the growth plate is restricted to the proliferative zone and is downregulated as chondrocyte maturation begins. Nkx3.2/Bapx1 expression is lost in the growth plates of mice engineered to lack PTHrP signaling and, conversely, is maintained by ectopic expression of PTHrP in developing bones. Artificially preventing Nkx3.2/Bapx1 downregulation, by forced expression of either retroviral-encoded PTHrP or Nkx3.2 inhibits chondrocyte maturation. Although wild-type Nkx3.2 blocks chondrocyte maturation by acting as a transcriptional repressor, a 'reverse function' mutant of Nkx3.2 that has been converted into a transcriptional activator conversely accelerates chondrocyte maturation. Nkx3.2 represses expression of the chondrocyte maturation factor Runx2, and Runx2 misexpression can rescue the Nkx3.2-induced blockade of chondrocyte maturation. Taken together, these results suggest that PTHrP signals block chondrocyte hypertrophy by, in part, maintaining the expression of Nkx3.2/Bapx1, which in turn represses the expression of genes required for chondrocyte maturation.

Original languageEnglish
Pages (from-to)651-662
Number of pages12
JournalDevelopment
Volume133
Issue number4
DOIs
Publication statusPublished - 2006 Feb

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Nkx3.2/Bapx1 acts as a negative regulator of chondrocyte maturation'. Together they form a unique fingerprint.

  • Cite this

    Provot, S., Kempf, H., Murtaugh, L. C., Chung, U. I., Kim, D. W., Chyung, J., Kronenberg, H. M., & Lassar, A. B. (2006). Nkx3.2/Bapx1 acts as a negative regulator of chondrocyte maturation. Development, 133(4), 651-662. https://doi.org/10.1242/dev.02258