title: Comparative effects of anti-inflammatory corticosteroids in human bone-derived osteoblast-like cells.
abstract: While effects of inhaled corticosteroids on serum markers of bone metabolism in normal and asthmatic subjects have been reported, there are little data on the direct effects of these corticosteroids on end-organs such as bone. The results presented here compare the effects of budesonide and its epimers (22S- and 22R-budesonide), fluticasone and dexamethasone on growth and differentiation of cultured human bone cells. Osteoblast-like cells were cultured from human foetal bone chips grown to confluence and used at first subculture. At concentrations of 10(-11)-10(-7) M each corticosteroid (CS) caused a dose-dependent decrease in [3H]thymidine incorporation into deoxyribonucleic acid (DNA), median effective concentration (EC50): fluticasone (0.06 nM) >22R (0.26 nM) >22S (0.4 nM) >budesonide (0.47 nM) >dexamethasone (1.5 nM). Each CS resulted in a dose-dependent increase in alkaline phosphatase activity, EC50: fluticasone (0.14 nM) >22R (0.2 nM)=22S (0.2 nM) >budesonide (0.4 nM) >dexamethasone (1.6 nM). The 1,25 dihydroxyvitamin D3 (1,25(OH)2D3)-stimulated osteocalcin production was decreased in the presence of each CS, EC50: fluticasone (0.02 nM) >22S (0.1 nM) >22R (0.2 nM) >budesonide (1.0 nM) >dexamethasone (1.8 nM). In human bone cells the potencies of fluticasone and budesonide in relation to dexamethasone are not dissimilar to those derived from human lymphocytes in vitro.
authors.affiliation: Dept of Physiology and Institute for Biomedical Research, University of Sydney, NSW Australia.
authors.forename: H
authors.initials: H
authors.lastname: Namkung-Matthäi
authors.forename: J P
authors.initials: JP
authors.lastname: Seale
authors.forename: K
authors.initials: K
authors.lastname: Brown
authors.forename: R S
authors.initials: RS
authors.lastname: Mason
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D019819:Budesonide / Q000031:analogs & derivatives / Q000494:pharmacology*; D002117:Calcitriol / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005333:Fetus; D000068298:Fluticasone; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000096:biosynthesis; D013936:Thymidine / Q000378:metabolism
chemical_list: D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D015675:Osteocalcin; D019819:Budesonide; D003907:Dexamethasone; D004247:DNA; D000068298:Fluticasone; D000469:Alkaline Phosphatase; D002117:Calcitriol; D013936:Thymidine