Cortisol decreases hepatocyte growth factor levels in human osteoblast-like cells.

Osteoporosis is a well-known side effect of long-term treatment with glucocorticoids. The hepatocyte growth factor (HGF) receptor is expressed by human osteoclasts and osteoblasts, and mouse osteoblasts also express HGF, indicating that HGF may regulate bone metabolism. Because HGF could be a candidate factor in the local paracrine signaling between osteoblasts and osteoclasts in bone, we decided to study whether human osteoblasts secrete HGF and whether glucocorticoids regulate the expression of HGF. HGF was easily detectable in the culture medium from human osteoblast-like cells (hOB). The HGF protein released into the culture medium was increased with increasing confluency. Hydrocortisone decreased the amount of HGF released into the culture medium from hOB in a dose-dependent manner with a maximal effect at 10(-6) M. Time-course studies revealed that hydrocortisone decreased the amount of HGF released into the culture medium significantly after 16 hours of stimulation (65 +/- 2% of control culture). This effect of hydrocortisone was maximal after 24 hours of stimulation (52 +/- 8% of control culture). In conclusion, HGF is produced by primary cultured hOB cells. Furthermore, the amount of HGF released into the culture medium is decreased by glucocorticoids. The biological significance of this finding remains to be demonstrated.