Runx/Smads interaction is impaired in osteoblasts from Fgf2-/- mice

Bone morphogenetic protein 2 (BMP2) is one of the most potent regulator of osteoblast differentiation and bone formation. R-Smads (Smads 1/5/8) are the major transducers for BMPs receptors and, once activated, they translocated in the nucleus regulating transcription target genes by interacting with various transcription factors (1). Runx2 proteins have been shown to interact through their C-terminal segment with Smads and this interaction is required for in vivo osteogenesis (2). In particular, recruitment of Smads to intranuclear sites is Runx2 dependent, and Runx2 factor may accommodate the dynamic targeting of signal transducer to active transcription sites (3). Previously, we have shown, by in vitro and in vivo experiments, that BMP2 up-regulated FGF-2 which is important for the maximal responses of BMP-2 in bone (4). Now, by biochemical, immunofluorescence and immunoelectron microscopy approaches, we found that BPM2 was also able to induce nuclear accumulation and colocalization of Runx2 and Smads1/5/8 in presence of endogenous FGF-2, while Runx/Smads nuclear interaction was markedly reduced in Fgf2-/- osteoblasts. Based on these preliminary data, we hypothesize that the impaired nuclear accumulation of Runx2 in Fgf2-/- osteoblasts could reduce R-Smads sub-nuclear targeting with a consequent decreased expression of differentiating markers and impaired bone formation in Fgf2 null mice.