Non-genomic mechanisms of vitamin D-regulated bone formation in osteoblasts

Zanello, Laura P. (2006) Non-genomic mechanisms of vitamin D-regulated bone formation in osteoblasts. Clinical cases in mineral and bone metabolism, 3 (2). pp. 50-57. ISSN 1971-3266

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Abstract

Hormone 1α,25(OH)2-vitamin D3 (1,25D) is considered a bone anabolic hormone. It increases bone matrix production and mineralization via the nuclear vitamin D receptor (VDR), which is abundantly expressed in osteoblasts. In addition, 1,25D exerts rapid, non-genomic actions that do not involve gene transactivation (1). These include: 1) activation of signal transduction pathways, 2) cytoplasmic Ca2+ increase, and 3) ion channel potentiation. While genomic mechanisms have been extensively studied, the signaling involved in non-genomic, membrane-initiated 1,25D actions is less well understood. Moreover, the physiological significance of 1,25D non-genomic effects in osteoblasts and its contribution to bone formation is a field relatively unexplored. Recently we demonstrated, for the first time in single live osteoblasts, a rapid (1-5 min) 1,25Dinduced increase of chloride currents at depolarizing potentials (2, 3). This voltage-gated Cl- channel is selectively potentiated by 1,25D (0.5-50 nM) in osteoblasts expressing a functional VDR (4). We showed that this 1,25D-induced Cl- current develops simultaneously with activation of exocytosis in single osteoblasts (5). In addition, nanomolar concentrations of 1,25D activate L-type calcium channels at low depolarizing potentials. These contribute to a rapid increase in cytoplasmic Ca2+ concentration promoted by the hormone. The purpose of this paper is to overview the current understanding on molecular mechanisms of non-genomic 1,25D-mediated processes of bone formation in osteoblasts. We found that 1,25D acting at a membrane-associated VDR leads to a rapid, regulated exocytotic response that is coupled to Cl- and Ca2+ channel activation in osteoblasts and explains in part the anabolic effects of the hormone in bone.

Item Type:	Article
Uncontrolled Keywords:	Osteoblasts, vitamin D3, rapid responses, ion channels, exocytosis
Subjects:	600 Tecnologia - Scienze applicate > 610 Medicina e salute (Classificare qui la tecnologia dei servizi medici) > 612 Fisiologia umana > 612.7 Sistema muscoloscheletrico, tegumento
Depositing User:	Danilo Dezzi
Date Deposited:	24 Jan 2014 11:52
Last Modified:	24 Jan 2014 11:52
URI:	http://eprints.bice.rm.cnr.it/id/eprint/4683

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