FGF-2 acts through an ERK1/2 intracellular pathway to affect osteoblast differentiation.

Abstract

An abundance of genetic and experimental data have suggested that fibroblast growth factor (FGF) signaling plays a central role in physiological and pathological cranial suture fusion. Although alterations in the differentiation and proliferation of sutural osteoblasts may be a key mediator of this process, the mechanisms by which FGF signaling regulates osteoblast differentiation remain incompletely understood. In the current study, the authors show that recombinant human FGF-2 alters osteoblastic expression of bone morphogenetic protein-2 and Msx-2 in vitro to favor cellular differentiation and osteoinduction. The ERK1/2 intracellular signaling cascade was shown to be necessary for recombinant human FGF-2-mediated bone morphogenetic protein-2 transcriptional changes. Furthermore, the cellular production of an intermediate transcriptional modifier was found to be necessary for the recombinant human FGF-2-mediated gene expression changes in bone morphogenetic protein-2 and Msx-2. Together, these findings offer new insight into the mechanisms by which FGF-2 modulates osteoblast biology.