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钙化二醇对人前成骨细胞的体外非基因组效应。

In Vitro Non-Genomic Effects of Calcifediol on Human Preosteoblastic Cells.

机构信息

Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.

Fondazione Italiana Ricerca Sulle Malattie dell'Osso (FIRMO Onlus), 50141 Florence, Italy.

出版信息

Nutrients. 2021 Nov 25;13(12):4227. doi: 10.3390/nu13124227.

Abstract

Several recent studies have demonstrated that the direct precursor of vitamin D, the calcifediol [25(OH)D], through the binding to the nuclear vitamin D receptor (VDR), is able to regulate the expression of many genes involved in several cellular processes. Considering that itself may function as a VDR ligand, although with a lower affinity, respect than the active form of vitamin D, we have assumed that 25(OH)D by binding the VDR could have a vitamin's D activity such as activating non-genomic pathways, and in particular we selected mesenchymal stem cells derived from human adipose tissue (hADMSCs) for the in vitro assessment of the intracellular Ca mobilization in response to 25(OH)D. Our result reveals the ability of 25(OH)D to activate rapid, non-genomic pathways, such as an increase of intracellular Ca levels, similar to what observed with the biologically active form of vitamin D. hADMSCs loaded with Fluo-4 AM exhibited a rapid and sustained increase in intracellular Ca concentration as a result of exposure to 10 M of 25(OH)D. In this work, we show for the first time the in vitro ability of 25(OH)D to induce a rapid increase of intracellular Ca levels in hADMSCs. These findings represent an important step to better understand the non-genomic effects of vitamin D and its role in endocrine system.

摘要

几项最近的研究表明,维生素 D 的直接前体,即 25-羟维生素 D [25(OH)D],通过与核维生素 D 受体 (VDR) 结合,能够调节涉及多种细胞过程的许多基因的表达。考虑到 25(OH)D 本身可能作为 VDR 配体发挥作用,尽管亲和力低于维生素 D 的活性形式,我们假设 25(OH)D 通过与 VDR 结合可能具有维生素 D 活性,例如激活非基因组途径,特别是我们选择了来源于人脂肪组织的间充质干细胞(hADMSCs),用于评估 25(OH)D 对细胞内 Ca 动员的体外反应。我们的结果揭示了 25(OH)D 激活快速非基因组途径的能力,例如增加细胞内 Ca 水平,类似于观察到的维生素 D 的生物活性形式。用 Fluo-4 AM 负载的 hADMSCs 由于暴露于 10 M 的 25(OH)D 而表现出细胞内 Ca 浓度的快速和持续增加。在这项工作中,我们首次展示了 25(OH)D 在体外诱导 hADMSCs 细胞内 Ca 水平快速增加的能力。这些发现代表了更好地理解维生素 D 的非基因组效应及其在内分泌系统中的作用的重要一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e72c/8707877/c6dcac3f33c8/nutrients-13-04227-g001.jpg

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