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Biol Pharm Bull. 2011;34(5):700-3.

Hydrocortisone inhibits cellular proliferation by downregulating hepatocyte growth factor synthesis in human osteoblasts.

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  • 1Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan.

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.

PMID:
21532160
[PubMed - indexed for MEDLINE]
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