Microarray analysis of Tbx2-directed gene expression: A possible role in osteogenesis

Jung Ren Chen, Qing Zhong, Jian Wang, Richard S. Cameron, James L. Borke, Carlos M. Isales, Roni J. Bollag

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Tbx2 is a member of the developmentally important transcriptional regulatory T-box gene family, whose target genes have not been well characterized. In an attempt to identify genes that may be regulated by Tbx2, mouse cDNA microarrays were used to analyze differential gene expression profiles, comparing stably transfected NIH3T3 cells overexpressing Tbx2 and vector-transfected controls. Among 8734 genes, 107 genes were up-regulated by 2-fold or greater, and 66 genes were down-regulated by 2-fold or greater. Caveolin, pleiotrophin (osf-1), osteoblast-specific factor-2 (osf-2) and collagen type Iα were among the genes upregulated in the Tbx2-overexpressing cells, whereas cadherin 3, tenascin C, and insulin-like growth factor binding protein 10/CYR61 (IBP10) were among the genes downregulated. Northern blot analysis confirmed the correlation of expression of several genes, including IBP10 and osf-2, in fibroblast NIH3T3 and rat osteosarcoma ROS17/2.8 cells differentially expressing Tbx2. In ROS17/2.8 cells transfected with antisense Tbx2, osf-2 was downregulated, whereas transfection of sense Tbx2 upregulated this gene. Interestingly, the expression of pleiotrophin (osf-1) and collagen Iα with Tbx2 transfection showed an inverse regulatory correlation between NIH3T3 and ROS17/2.8 cells. Thus, Tbx2 can act as both a repressor and activator, and the cellular context can influence the effect on gene expression. Although the data do not address whether Tbx2 directly mediates the transcriptional effect, a number of candidate genes possess putative T-box gene regulatory elements. The results support the hypothesis that Tbx2 may be an important modulator of bone development. Further functional cluster analysis indicates that Tbx2 might also be involved in the regulation of cell cycle and cell adhesion.

Original languageEnglish (US)
Pages (from-to)43-54
Number of pages12
JournalMolecular and Cellular Endocrinology
Volume177
Issue number1-2
DOIs
StatePublished - May 25 2001

Fingerprint

Microarray Analysis
Microarrays
Osteogenesis
Gene expression
Genes
Gene Expression
Osteoblasts
Insulin-Like Growth Factor Binding Proteins
Transfection
Down-Regulation
Caveolins
Tenascin
Bone Development
Osteosarcoma
Cadherins
Regulator Genes
Collagen Type I
Oligonucleotide Array Sequence Analysis
Transcriptome
Cell Adhesion

Keywords

  • Bone
  • Cartilage
  • Cell adhesion
  • Cell cycle
  • Gene expression
  • Microarray
  • T-box genes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

Microarray analysis of Tbx2-directed gene expression : A possible role in osteogenesis. / Chen, Jung Ren; Zhong, Qing; Wang, Jian; Cameron, Richard S.; Borke, James L.; Isales, Carlos M.; Bollag, Roni J.

In: Molecular and Cellular Endocrinology, Vol. 177, No. 1-2, 25.05.2001, p. 43-54.

Research output: Contribution to journalArticle

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