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

78 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 1

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Chondrocytes
Parathyroid Hormone-Related Protein
Growth Plate
Down-Regulation
Bone and Bones
Hypertrophy
Gene Expression

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

Cite this

Provot, S., Kempf, H., Murtaugh, L. C., Chung, U. I., Kim, D. W., Chyung, J., ... 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
Provot, Sylvain ; Kempf, Hervé ; Murtaugh, L. Charles ; Chung, Ung Il ; Kim, Dae Won ; Chyung, Jay ; Kronenberg, Henry M. ; Lassar, Andrew B. / Nkx3.2/Bapx1 acts as a negative regulator of chondrocyte maturation. In: Development. 2006 ; Vol. 133, No. 4. pp. 651-662.
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Provot, S, Kempf, H, Murtaugh, LC, Chung, UI, Kim, DW, Chyung, J, Kronenberg, HM & Lassar, AB 2006, 'Nkx3.2/Bapx1 acts as a negative regulator of chondrocyte maturation', Development, vol. 133, no. 4, pp. 651-662. https://doi.org/10.1242/dev.02258

Nkx3.2/Bapx1 acts as a negative regulator of chondrocyte maturation. / Provot, Sylvain; Kempf, Hervé; Murtaugh, L. Charles; Chung, Ung Il; Kim, Dae Won; Chyung, Jay; Kronenberg, Henry M.; Lassar, Andrew B.

In: Development, Vol. 133, No. 4, 01.02.2006, p. 651-662.

Research output: Contribution to journalArticle

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Provot S, Kempf H, Murtaugh LC, Chung UI, Kim DW, Chyung J et al. Nkx3.2/Bapx1 acts as a negative regulator of chondrocyte maturation. Development. 2006 Feb 1;133(4):651-662. https://doi.org/10.1242/dev.02258