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

Anita Borton Hjelmeland, Stephen H. Schilling, Xing Guo, Leigh Quarles, Xiao Fan Wang

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)9460-9468
Number of pages9
JournalMolecular and cellular biology
Volume25
Issue number21
DOIs
StatePublished - Nov 1 2005

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Osteoblasts
Fibroblasts
Skin
Calcium
Phenotype
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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Loss of Smad3-mediated negative regulation of Runx2 activity leads to an alteration in cell fate determination. / Hjelmeland, Anita Borton; Schilling, Stephen H.; Guo, Xing; Quarles, Leigh; Wang, Xiao Fan.

In: Molecular and cellular biology, Vol. 25, No. 21, 01.11.2005, p. 9460-9468.

Research output: Contribution to journalArticle

Hjelmeland, Anita Borton ; Schilling, Stephen H. ; Guo, Xing ; Quarles, Leigh ; Wang, Xiao Fan. / Loss of Smad3-mediated negative regulation of Runx2 activity leads to an alteration in cell fate determination. In: Molecular and cellular biology. 2005 ; Vol. 25, No. 21. pp. 9460-9468.
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