Bone morphogenetic protein-2 (BMP-2) signaling to the Col2α1 gene in chondroblasts requires the homeobox gene Dlx-2

S. C. Xu, M. A. Harris, J. L.R. Rubenstein, G. R. Mundy, S. E. Harris

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

To understand the role of Dlx genes in the process of chondrogenesis, we studied the expression of Dlx-2 and Dlx-5 mRNAs in a mouse clonal chondroblast cell line, TMC23. We also examined the involvement of Dlx2 in the bone morphogenetic protein-2 (BMP-2) signaling to the type II collagen gene, Col2α1, in this cell line. In this report, we show that the TMC23 cells expresse Dlx-2 and Dlx-5 mRNAs, and the levels can be upregulated by recombinant BMP-2 at an early stage of chondroblast differentiation. Addition of rBMP-2 dramatically increased type II collagen expression at both the mRNA and the protein level. Also, rBMP-2 increased transcription of Col2α1, as shown by stimulation of a chondrocyte-specific Col2α1 enhancer. The mechanism involves Dlx-2, as the stimulatory effect of rBMP-2 on the Col2α1 enhancer was blocked by an antisense oligonucleotide against Dlx-2 mRNA. The rBMP-2 signaling to the Col2α1 enhancer was also blocked by a dominant-negative Smad1 expression vector. These data demonstrate that Dlx-2 is a downstream target of the BMP-2 signaling pathway in chondroblasts. Therefore, we propose a model in which rBMP-2 stimulates Dlx-2 expression, which then serves as a necessary transcription factor for Col2α1 gene expression through a chondrocyte-specific enhancer fragment.

Original languageEnglish (US)
Pages (from-to)359-365
Number of pages7
JournalDNA and Cell Biology
Volume20
Issue number6
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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