title: FGF-2 enhances Runx-2/Smads nuclear localization in BMP-2 canonical signaling in osteoblasts.
abstract: Bone morphogenetic protein 2 (BMP-2) is one of the most potent regulators of osteoblast differentiation and bone formation. R-Smads (Smads 1/5/8) are the major transducers for BMPs receptors and, once activated, they are translocated in the nucleus regulating transcription target genes by interacting with various transcription factors. Runx-2 proteins have been shown to interact through their C-terminal segment with Smads and this interaction is required for in vivo osteogenesis. In particular, recruitment of Smads to intranuclear sites is Runx-2 dependent, and Runx-2 factor may accommodate the dynamic targeting of signal transducer to active transcription sites. Previously, we have shown, by in vitro and in vivo experiments, that BMP-2 up-regulated FGF-2 which is important for the maximal responses of BMP-2 in bone. In this study, we found that endogenous FGF2 is necessary for BMP-2 induced nuclear accumulation and co-localization of Runx-2 and phospho-Smads1/5/8, while Runx/Smads nuclear accumulation and co-localization was reduced in Fgf2-/- osteoblasts. Based on these novel data, we conclude that the impaired nuclear accumulation of Runx-2 in Fgf2-/- osteoblasts reduces R-Smads sub-nuclear targeting with a consequent decreased expression of differentiating markers and impaired bone formation in Fgf2 null mice.
authors.affiliation: School of Biosciences and Biotechnology, University of Camerino, Camerino, Macerata, Italy.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Agas
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Sabbieti
authors.forename: Luigi
authors.initials: L
authors.lastname: Marchetti
authors.forename: Liping
authors.initials: L
authors.lastname: Xiao
authors.forename: Marja M
authors.initials: MM
authors.lastname: Hurley
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000172:deficiency / Q000378:metabolism*; D005453:Fluorescence; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D012886:Skull / Q000166:cytology; D051785:Smad Proteins / Q000378:metabolism*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
chemical_list: D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D051785:Smad Proteins; D016222:Fibroblast Growth Factor 2; D051057:Proto-Oncogene Proteins c-akt