Regulation of NFATc2 gene expression by the transcription factor Runx2

Abstract

NFATc2 is a transcription factor that has been shown to function as a repressor of cartilage cell growth and differentiation in mice. In order to understand the transcriptional regulation of NFATc2 gene expression, we have cloned and characterized approximately 2.5 kb 5'-flanking regions of the mouse and human NFATc2 genes. Sequence analysis of the promoters revealed putative binding sites for the Runx family of transcription factors, of which one member, Runx2, plays a key role in chondrocyte maturation and osteoblast differentiation. Using promoter-reporter assays we have shown that Runx2 overexpression results in a significant increase in NFATc2 transactivation in fibroblastic, mesenchymal and chondrocytic cells. Runx2 overexpression also resulted in a substantial increase in endogenous NFATc2 mRNA levels in C3H10T1/2 mesenchymal cells implicating the NFATc2 gene as a potential downstream target of Runx2. Our results suggest that the role of Runx2 in promoting chondrocyte maturation and hypertrophy may be mediated, at least in part, via the stimulation of NFATc2 expression.