title: Hydrocortisone inhibits cellular proliferation by downregulating hepatocyte growth factor synthesis in human osteoblasts.
abstract: Glucocorticoids have multiple systemic effects that may influence bone metabolism but also directly affect osteoblasts by decreasing their proliferation. Using human osteoblastic SaM-1 cells, we examined whether the effects of hydrocortisone on cellular proliferation are mediated by hepatocyte growth factor (HGF). Human osteoblasts constitutively express both HGF and c-Met, its receptor. Hydrocortisone decreased the gene and protein expression of HGF as well as proliferation in SaM-1 cells. These hydrocortisone (0.01-1 µM)-induced decreases in HGF synthesis and cellular proliferation occurred in a concentration-dependent manner. However, no hydrocortisone (0.01-1 µM)-induced decrease in cellular proliferation was observed in human osteosarcoma-derived cells (HOS and SaOS-2), which are not able to produce HGF. In the cellular proliferation in SaM-1 cells, the decrease was blocked concentration-dependently by exogenously applied HGF (0.01-3 ng/ml). Furthermore, SU11274 (1 µM), a highly specific inhibitor of c-Met, suppressed the proliferation of SaM-1 cells, but not HOS cells. From these results, we concluded that hydrocortisone inhibits the proliferation of SaM-1 cells by interrupting the autocrine/paracrine loop via the downregulation of HGF synthesis.
authors.affiliation: Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Tsunashima
authors.forename: Ayami
authors.initials: A
authors.lastname: Kondo
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsuda
authors.forename: Akifumi
authors.initials: A
authors.lastname: Togari
mesh_terms: D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects*; D017931:DNA Primers; D015536:Down-Regulation / Q000187:drug effects*; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D017228:Hepatocyte Growth Factor; D006854:Hydrocortisone