The Sox2 high mobility group transcription factor inhibits mature osteoblast function in transgenic mice

Greg Holmes, Timothy Bromage, Claudio Basilico

Research output: Contribution to journalArticle

Abstract

We have previously shown that in osteoblasts Sox2 expression can be induced by Fgfs, and can inhibit Wnt signaling and differentiation. Furthermore, in mice in which Sox2 is conditionally deleted in the osteoblastic lineage, bones are osteopenic, and Sox2 inactivation in cultured osteoblasts leads to a loss of proliferative ability with a senescent phenotype. To help understand the role of Sox2 in osteoblast development we have specifically expressed Sox2 in bone from a Col1-1 promoter, which extended Sox2 expression into more mature osteoblasts. In long bones, trabecular cartilage remodeling was delayed and the transition from endochondral to cortical bone was disrupted, resulting in porous and undermineralized cortical bone. Collagen deposition was disorganized, and patterns of osteoclast activity were altered. Calvarial bones were thinner and parietal bones failed to develop the diploic space. Microarray analysis showed significant up- or downregulation of a variety of genes coding for non-collagenous extracellular matrix proteins, with a number of genes typical of mature osteoblasts being downregulated. Our results position Sox2 as a negative regulator of osteoblast maturation in vivo.

Original languageEnglish (US)
Pages (from-to)653-661
Number of pages9
JournalBone
Volume49
Issue number4
DOIs
StatePublished - Oct 2011

Fingerprint

Osteoblasts
Transgenic Mice
Transcription Factors
Bone and Bones
Down-Regulation
Parietal Bone
Extracellular Matrix Proteins
Osteoclasts
Microarray Analysis
Genes
Cartilage
Up-Regulation
Collagen
Phenotype

Keywords

  • Bone
  • Differentiation
  • Osteoblasts
  • Sox2
  • Transgenic

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

Cite this

The Sox2 high mobility group transcription factor inhibits mature osteoblast function in transgenic mice. / Holmes, Greg; Bromage, Timothy; Basilico, Claudio.

In: Bone, Vol. 49, No. 4, 10.2011, p. 653-661.

Research output: Contribution to journalArticle

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