Runx2 regulates diverse gene expression programs to (de‐) sensitize the osteogenic and/or mitogenic responses of osteoblast progenitors and osteosarcoma cells

Abstract

The osteogenic and cell cycle regulatory functions of Runt‐related transcription factor 2 (Runx2) are perturbed in osteosarcoma cells. We investigated which target genes of Runx2 control proliferation of normal osteoblasts and osteosarcoma cells by Affymetrix expression profiling and ChIP‐on‐chip analysis using NimbleGen arrays. Target gene analysis shows that Runx2 modulates normal osteoblast proliferation by regulating distinct programs of genes involved in G protein‐coupled receptor signaling, sterol/steroid metabolism, the fibroblast growth factor/proteoglycan signaling axis, RNA helicases and heat shock proteins. Strikingly, our data reveal that the gene expression programs controlled by Runx2 in osteoprogenitors are fundamentally different from those in osteosarcomas. Thus cancer‐related perturbations in normal osteoblast growth and differentiation switch the biological function of Runx2 from a growth suppressor to a putative oncoprotein that supports the tumorigenic and/or metastatic potential of osteosarcoma cells.