Abstract
BackgroundWe previously demonstrated that 25-hydroxyvitamin D3, the precursor of 1α,25-dihydroxyvitamin D3, is abundant around periodontal soft tissues. Here we investigate whether 25-hydroxyvitamin D3 is converted to 1α,25-dihydroxyvitamin D3 in periodontal soft tissue cells and explore the possibility of an autocrine/paracrine function of 1α,25-dihydroxyvitamin D3 in periodontal soft tissue cells.Methodology/Principal FindingsWe established primary cultures of human gingival fibroblasts and human periodontal ligament cells from 5 individual donors. We demonstrated that 1α-hydroxylase was expressed in human gingival fibroblasts and periodontal ligament cells, as was cubilin. After incubation with the 1α-hydroxylase substrate 25-hydroxyvitamin D3, human gingival fibroblasts and periodontal ligament cells generated detectable 1α,25-dihydroxyvitamin D3 that resulted in an up-regulation of CYP24A1 and RANKL mRNA. A specific knockdown of 1α-hydroxylase in human gingival fibroblasts and periodontal ligament cells using siRNA resulted in a significant reduction in both 1α,25-dihydroxyvitamin D3 production and mRNA expression of CYP24A1 and RANKL. The classical renal regulators of 1α-hydroxylase (parathyroid hormone, calcium and 1α,25-dihydroxyvitamin D3) and Porphyromonas gingivalis lipopolysaccharide did not influence 1α-hydroxylase expression significantly, however, interleukin-1β and sodium butyrate strongly induced 1α-hydroxylase expression in human gingival fibroblasts and periodontal ligament cells.Conclusions/SignificanceIn this study, the expression, activity and functionality of 1α-hydroxylase were detected in human gingival fibroblasts and periodontal ligament cells, raising the possibility that vitamin D acts in an autocrine/paracrine manner in these cells.
Highlights
Vitamin D3 is a major component in the regulation of calcium and phosphorus metabolism
The 1,25OH2D3 produced by Human gingival fibroblasts (hGF) and human periodontal ligament cells (hPDLC) can influence vitamin D-responsive gene expression (Fig. 4, 7), an observation that provides a solid indication of an autocrine/ paracrine action of vitamin D in periodontal fibroblasts
Because metabolism of 25OHD3 and 1,25OH2D3 by CYP24A1 is very important in the autocrine/paracrine action of vitamin D, we investigated the time course of CYP27B1 and CYP24A1 mRNA expression
Summary
Vitamin D3 is a major component in the regulation of calcium and phosphorus metabolism. The function of vitamin D3, via the active hormonal metabolite 1a,25-dihydroxyvitamin D3 (1,25OH2D3), is to regulate the absorption of these essential minerals in the intestine, and their mobilization in bone tissues [1]. The biological function of 1,25OH2D3 is orchestrated by vitamin D receptor (VDR). After binding with VDR, 1,25OH2D3 acts on the vitamin D responsive element (VDRE) located upstream of its target genes Besides the kidney [9,10,11], there are extra-renal sites of 1,25OH2D3 synthesis, including the skin [12], prostate [13], activated monocytes/macrophages [14], bone [15,16] and sebocytes [17]. Local production of 1,25OH2D3 in extrarenal tissues has been postulated to regulate parameters of cell growth and differentiation in an autocrine or paracrine fashion [15,18]. We investigate whether 25-hydroxyvitamin D3 is converted to 1a,25dihydroxyvitamin D3 in periodontal soft tissue cells and explore the possibility of an autocrine/paracrine function of 1a,25dihydroxyvitamin D3 in periodontal soft tissue cells
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