Fibroblast growth factor-2 induces hepatocyte growth factor/scatter factor expression in osteoblasts

Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional growth factor with a major role in tissue morphogenesis and repair. It stimulates the proliferation of cells of the osteoblast and osteoclast lineages. Mitogenic factors playing a role in fracture repair may act by regulating HGF/SF expression or activity in bone-forming cells. We investigated the effect of fibroblast growth factor-2 (FGF-2) on the expression of HGF/SF and its receptor, encoded by c-met, in the MC3T3-E1 osteoblastic cell line. MC3T3-E1 cells expressed low levels of HGF/SF messenger RNA (mRNA), which were markedly increased by FGF-2 in a dose- and time-dependent manner. FGF-2 also induced HGF/SF polypeptide synthesis. The stimulation of HGF/SF mRNA expression by FGF-2 was blocked by cycloheximide, a protein synthesis inhibitor, but not by DNA or prostaglandin synthesis inhibitors. FGF-2 increased the rate of HGF/SF gene transcription by approximately 2-fold, as determined by nuclear run-on assays, and did not modify the decay of HGF/SF mRNA in transcriptionally arrested cells. FGF-2 also caused a dose- and time-dependent stimulation of c-met mRNA. In conclusion, FGF-2 induces HGF/SF expression in osteoblasts and may promote HGF/SF activity by increasing the expression of its receptor. Through these mechanisms, HGF/SF could mediate FGF actions on bone repair.