THE RAPID NONGENOMIC ACTIONS OF 1-ALPHA,25-DIHYDROXYVITAMIN-D3 MODULATE THE HORMONE-INDUCED INCREMENTS IN OSTEOCALCIN GENE-TRANSCRIPTION IN OSTEOBLAST-LIKE CELLS

We have previously shown that one of the rapid nongenomic actions of 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3), the increase in intracellular calcium (Ca2+), accompanies the increased osteocalcin (OC) mRNA steady-state levels in rat osteosarcoma cells. To determine the functional significance of the nongenomic actions, we have measured changes in intracellular Ca2+ as an indicator of the rapid effects and have assessed the effect of inhibition of the rapid increase in cellular Ca2+ by the inactive epimer, 1beta,25-dihydroxyvitamin D3 (1beta,25-(OH)2D3), on OC mRNA steady-state levels and transcription. 1beta,25-dihydroxyvitamin D3 inhibited 1alpha,25-(OH)2D3 induced increases in intracellular Ca2+ and OC mRNA transcription at 1 hr and OC mRNA steady state levels at 3 hr. 1beta,25-Dihydroxyvitamin D3 did not alter the binding of the vitamin D receptor complex to the vitamin D responsive element of the OC gene. The results demonstrate the functional importance of the rapid, nongenomic actions of 1alpha,25-(OH)2D3 in the genomic activation of the OC gene by the hormone in rat osteoblast-like cells, perhaps by modifying subtle structural and/or functional properties of the vitamin D-receptor DNA complex or by affecting other protein DNA interactions that support OC gene transcription.