Loss of Smad3-mediated negative regulation of Runx2 activity leads to an alteration in cell fate determination.

Journal Article (Journal Article)

Runx2 is required for osteoblast differentiation but is expressed in certain nonosteoblastic cells without activating the differentiation process, suggesting that its activity is suppressed through a lineage-specific mechanism. Here we report that primary mouse dermal fibroblasts lacking Smad3 can acquire an osteoblast-like phenotype, including activation of Runx2 activity, expression of osteoblast-specific genes, and calcium deposition. We further show that negative regulation of Runx2 activity by Smad3 in dermal fibroblasts is likely mediated by controlling the expression of Msx2, an antagonist of Runx2 in this cellular context. These data support the presence of a novel mechanism for controlling cell fate determination of mesenchymal lineages by preventing differentiation toward the osteoblastic lineage via negative regulation of Runx2 activity.

Full Text

Duke Authors

Cited Authors

  • Hjelmeland, AB; Schilling, SH; Guo, X; Quarles, D; Wang, X-F

Published Date

  • November 2005

Published In

Volume / Issue

  • 25 / 21

Start / End Page

  • 9460 - 9468

PubMed ID

  • 16227596

Pubmed Central ID

  • PMC1265845

International Standard Serial Number (ISSN)

  • 0270-7306

Digital Object Identifier (DOI)

  • 10.1128/MCB.25.21.9460-9468.2005


  • eng

Conference Location

  • United States