The rapid nongenomic actions of 1α,25-dihydroxyvitamin D3 modulate the hormone-induced increments in osteocalcin gene transcription in osteoblast-like cells

✍ Scribed by Daniel T. Baran; Ann Marie Sorensen; Victoria Shalhoub; Thomas Owen; Gary Stein; Jane Lian

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Volume: 50
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240500203

✦ Synopsis

Abstract

We have previously shown that one of the rapid nongenomic actions of 1α,25‐dihydroxyvitamin D~3~ (1α,25‐(OH)~2~D~3~), the increase in intracellular calcium (Ca^2+^), 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 Ca^2+^ as an indicator of the rapid effects and have assessed the effect of inhibition of the rapid increase in cellular Ca^2+^ by the inactive epimer, 1β,25‐dihydroxyvitamin D~3~ (1β,25‐(OH)~2~D~3~) on OC mRNA steady‐state levels and transcription. 1β,25‐dihydroxyvitamin D~3~ inhibited 1α,25‐(OH)~2~D~3~ induced increases in intracellular Ca^2+^ and OC mRNA transcription at 1 hr and OC mRNA steady state levels at 3 hr. 1β,25‐Dihydroxyvitamin D~3~ 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 1α,25‐(OH)~2~D~3~ 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. © 1992 Wiley‐Liss, Inc.