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Caffeine-mediated enhancement of glucocorticoid receptor activity in human osteoblastic cells

2005; Elsevier BV; Volume: 337; Issue: 2 Linguagem: Inglês

10.1016/j.bbrc.2005.09.067

1090-2104

Melanie Föcking, Diane Schmiegelt, Thorsten Trapp,

Reproductive System and Pregnancy

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.