Runx2 is a transcription factor that belongs to Runx family (Runx1, Runx2, and Runx3). Runx2 interacts with many other transcription factors and co-regulators in the transcriptional regulation of its target genes. Cbfb is one of the co-regulators, forms heterodimers with Runx2, and is required for Runx2-dependent transcriptional regulation. Runx2 is essential for the commitment of multipotent mesenchymal cells into the osteoblastic lineage, because Runx2-deficient mice show complete lack of bone formation due to the absence of osteoblasts. Further, Runx2 inhibits adipocyte differentiation, because Runx2-deficient calvarial cells spontaneously differentiate into adipocytes. Overexpression of Runx2 in osteoblasts inhibits osteoblast maturation but decreased the expression of major bone matrix protein genes. Therefore, Runx2 triggers the gene expression of bone matrix proteins, while keeping the osteoblastic cells in an immature stage. Moreover, Runx2 strongly inhibits the transition of osteoblasts into osteocytes. Runx2 and Runx3 double knockout mice showed that Runx2 and Runx3 have redundant functions in chondrocytes, and that they are essential for chondrocyte maturation. Runx2 directly induces Ihh expression and coordinates the proliferation and differentiation of chondrocytes. Therefore, Runx2 regulates bone formation by regulating osteoblast differentiation as well as chondrocyte maturation
