RUNX2 and osteosarcoma: Rb loss could hamper osteoblast differentiation and promote osteosarcoma formation by a two-fold effect, first, by compromising the transactivating capacity of Runx2 with consequent attenuation of bone-specific gene expression, and second, by compromising cell-to-cell interactions, which are recognized as major drivers of osteoblast differentiation [13, 51, 52, 53, 54].