The authors have no conflict of interest
Identification of Novel Target Genes of the Bone-Specific Transcription Factor Runx2†
Article first published online: 1 JUN 2004
Copyright © 2004 ASBMR
Journal of Bone and Mineral Research
Volume 19, Issue 6, pages 959–972, June 2004
How to Cite
Stock, M., Schäfer, H., Fliegauf, M. and Otto, F. (2004), Identification of Novel Target Genes of the Bone-Specific Transcription Factor Runx2. J Bone Miner Res, 19: 959–972. doi: 10.1359/jbmr.2004.19.6.959
- Issue published online: 2 DEC 2009
- Article first published online: 1 JUN 2004
- Manuscript Accepted: 13 FEB 2004
- Manuscript Revised: 29 DEC 2003
- Manuscript Received: 11 JUN 2003
- transcriptional regulation;
- selective amplification through biotin and restriction-mediated enrichment;
- cDNA microarray
Fifteen putative transcriptional target genes regulated by the osteogenic transcription factor Runx2 were identified by cDNA microarray and differential hybridization techniques. Expression pattern and regulation of one gene, Pttg1ip, was analyzed in detail.
Introduction: The transcription factor Runx2 is a key regulator of osteoblast development and plays a role in chondrocyte maturation. The identification of transcriptional target genes of Runx2 may yield insight into how osteoblastic differentiation is achieved on a molecular level.
Materials and Methods: Using a differential hybridization technique (selective amplification through biotin and restriction-mediated enrichment [SABRE]) and cDNA microarray analysis, 15 differentially expressed genes were identified using mRNA from C3H 10T1/2 cells with constitutive and inducible overexpression of Runx2.
Results and Conclusions: Among the 15 genes identified, 4 encode the extracellular matrix proteins Ecm1, Mgp, Fbn5, and Osf-2, three represent the transcription factors Esx1, Osr1, and Sox9, whereas others were Ptn, Npdc-1, Hig1, and Tem1. The gene for Pttg1ip was upregulated in Runx2-expressing cells. Pttg1ip is widely expressed during development, but at highest levels in limbs and gonads. The Pttg1ip promoter binds Runx2 in a sequence specific manner, and Runx2 is able to transactivate the Pttg1ip promoter in MC3T3-E1 cells. Therefore, Pttg1ip is likely to be a novel direct transcriptional target gene of Runx2. In conclusion, the genes identified in this study are important candidates for mediating Runx2 induced cellular differentiation.