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Abstract
<p class="first" id="d23379988e59">Osteoblasts are a main target for the steroid 1alpha,25(OH)2-Vitamin
D3 (1,25D3),
where a major outcome is the modulation of the bone remodeling process. 1,25D3 deficiency
leads to clinical disorders such as osteomalacia and osteoporosis, characterized by
a state of insufficiently calcified tissue and bone loss, respectively. In the osteoblast
nucleus, 1,25D3 modulates gene transcription for the synthesis of bone matrix proteins
via the Vitamin D receptor (VDR). At the plasma membrane level, 1,25D3 potentiates
ion channel functions, activates signal transduction pathways, and increases cytoplasmic
calcium concentrations. So far, no clear physiological significance has been attributed
to membrane-initiated 1,25D3 actions in single cells. To investigate if (a) 1,25D3
is a modulatory agent of secretion in osteoblasts and (b) the classical VDR is involved
in rapid electrical events in the cell membrane, we studied hormone effects on ion
channel activities in relation to exocytosis in osteoblasts isolated from VDR knockout
(KO) and wild-type (WT) mice. This paper is a retrospect of the electrophysiological
studies done in our laboratory to date. We found that 1,25D3-promoted ion channel
responses are coupled to secretion in calvarial osteoblasts, and develop only in the
presence of a functional nuclear steroid VDR. This 1,25D3-regulated exocytosis in
osteoblasts, which takes place within minutes of hormone application, seems to be
the natural complement of genomic actions that evolve at a longer time scale. The
absence of both 1,25D3 membrane and nuclear effects in VDR KO osteoblasts may explain
bone abnormalities typically found in VDR KO mice.
</p>