Action of Vitamin D and the Receptor, VDRa, in Calcium Handling in Zebrafish (Danio rerio)

The purpose of the present study was to use zebrafish as a model to investigate how vitamin D and its receptors interact to control Ca(2+) uptake function. Low-Ca(2+) fresh water stimulated Ca(2+) influx and expressions of epithelial calcium channel (ecac), vitamin D-25-hydroxylase (cyp2r1), vitamin D receptor a (vdra), and vdrb in zebrafish. Exogenous vitamin D increased Ca(2+) influx and expressions of ecac and 25-hydroxyvitamin D(3)-24-hydroxylase (cyp24a1), but downregulated 1α-OHase (cyp27b1) with no effects on other Ca(2+) transporters. Morpholino oligonucleotide knockdown of VDRa, but not VDRb, was found as a consequence of calcium uptake inhibition by knockdown of ecac, and ossification of vertebrae is impaired. Taken together, vitamin D-VDRa signaling may stimulate Ca(2+) uptake by upregulating ECaC in zebrafish, thereby clarifying the Ca(2+)-handling function of only a VDR in teleosts. Zebrafish may be useful as a model to explore the function of vitamin D-VDR signaling in Ca(2+) homeostasis and the related physiological processes in vertebrates.