Cortisol inhibits hepatocyte growth factor/scatter factor expression and induces c-met transcripts in osteoblasts

Hepatocyte growth factor/scatter factor (HGF/SF) is expressed by osteoblast s and has important effects on repair and bone remodeling. Because glucocor ticoids regulate these two functions, we tested the effects of cortisol on the expression of HGF/SF and c-met, the protooncogene encoding the HGF/SF r eceptor, in cultures of osteoblast-enriched cells from 22-day fetal rat cal variae (Ob cells). Cortisol decreased HGF/SF mRNA levels and diminished the induction of HGF/SF transcripts by fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor BE (PDGF BB). Cortisol also decreased FGF-2 and PDGF BB-induced HGF/SF mRNA and polypeptide levels in MC3T3 cells. In c ontrast, cortisol enhanced the expression of c-met transcripts in Ob cells. Cortisol did not modify the half-life of HGF/SF or of c-met mRNA in transc riptionally arrested cells, and it increased the rate of transcription of c -met. In conclusion, cortisol decreases HGF/SF transcripts in Ob cells and enhances c-met expression transcriptionally. The effects of cortisol on HGF /SF could be relevant to its inhibitory actions on bone formation and repai r.