Caffeine-mediated enhancement of glucocorticoid receptor activity in human osteoblastic cells.
Caffeine-containing beverage consumption has been reported to be associated with an increased risk for osteoporosis. Since the glucocorticoid receptor (GR) is a major factor in the induction of osteoporosis we analyzed whether caffeine may act via altering GR function. Applying a reporter gene assay we provide evidence that caffeine drastically amplifies GR transcriptional activity in human osteoblastic cells. Substances that increase the intracellular cyclic AMP-concentration also strengthen the transactivity of the GR and coincubation with caffeine further reinforces this potentiation, indicating that caffeine-mediated enhancement of GR transcriptional function is due to the inhibitory activity of caffeine on the cyclic AMP phosphodiesterase. Our data suggest evidence for a hitherto unrecognized crosstalk between caffeine-modulated signalling and GR-initiated gene expression in human osteoblastic cells and could provide the molecular basis for the role of caffeine in osteoporosis.
Föcking
Melanie
M
Max-Planck-Institute for Neurological Research, Cologne, Germany.
Schmiegelt
Diane
D
Trapp
Thorsten
T
D002110:Caffeine / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*
D010726:Phosphodiesterase Inhibitors; D011965:Receptors, Glucocorticoid; D002110:Caffeine; D000242:Cyclic AMP