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 osteoblasts and has important effects on repair and bone remodeling. Because glucocorticoids 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 receptor, in cultures of osteoblast-enriched cells from 22-day fetal rat calvariae (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 BB (PDGF BB). Cortisol also decreased FGF-2 and PDGF BB-induced HGF/SF mRNA and polypeptide levels in MC3T3 cells. In contrast, 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 transcriptionally 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 repair.
Blanquaert
F
F
Departments of Research and Medicine, Saint Francis Hospital and Medical Center, Hartford, CT 06105, USA.
Pereira
R C
RC
Canalis
E
E
D000818:Animals; D000077214:Becaplermin; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics; D006854:Hydrocortisone / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D012886:Skull / Q000166:cytology / Q000196:embryology; D014158:Transcription, Genetic / Q000187:drug effects*
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D006854:Hydrocortisone