Abstract

1?,25-dihydroxy vitamin D3 has a major role in the regulation of the bone metabolism as it promotes the expression of key bone-related proteins in osteoblastic cells. In recent years it has become increasingly evident that in addition to its well-established genomic actions, 1?,25-dihydroxy vitamin D3 induces non-genomic responses by acting through a specific plasma membrane-associated receptor. Results from several groups suggest that the classical nuclear 1?,25-dihydroxy vitamin D3 receptor (VDR) is also responsible for these non-genomic actions of 1?,25-dihydroxy vitamin D3. Here, we have used siRNA to suppress the expression of VDR in osteoblastic cells and assessed the role of VDR in the non-genomic response to 1?,25-dihydroxy vitamin D3. We report that expression of the classic VDR in osteoblasts is required to generate a rapid 1?,25-dihydroxy vitamin D3-mediated increase in the intracellular Ca 2+ concentration, a hallmark of the non-genomic actions of 1?,25-dihydroxy vitamin D3 in these cells. © 2006 Wiley-Liss, Inc.