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

Osteoporosis is a well-known side effect of longterm treatment with glucoco rticoids. The hepatocyte growth factor (HGF) receptor is expressed by human osteoclasts and osteoblasts, and mouse osteoblasts also express HGF, indic ating that HGF may regulate bone metabolism. Because HGF could be a candida te factor in the local paracrine signaling between osteoblasts and osteocla sts in bone, we decided to study whether human osteoblasts secrete HGF and whether glucocorticoids regulate the expression of HGF. HGF was easily dete ctable in the culture medium from human osteoblast-like cells (hOB). The HG F protein released into the culture medium was increased with increasing co nfluency. Hydrocortisone decreased the amount of HGF released into the cult ure medium from hOB in a dose-dependent manner with a maximal effect at 10( -6) M. Time-course studies revealed that hydrocortisone decreased the amoun t of HGF released into the culture medium significantly after 16 hours of s timulation (65 +/- 2% of control culture). This effect of hydrocortisone wa s 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 glucocortic oids. The biological significance of this finding remains to be demonstrate d.