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Magnesium in Differentiation and Development

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 59165

Special Issue Editors

1. Department of Pharmacy and Biotechnology, University of Bologna, 40127 Bologna, Italy
2. National Institute of Biostructures and Biosystems, 00136 Rome, Italy
Interests: biochemistry; biochemical thermodynamics; physical chemistry; cell imaging; science and art integration; effect of sound on living systems
Department of Biomedical and Clinical Sciences L. Sacco, University of Milano, Via GB Grassi, 74, 20157 Milano, Italy
Interests: pathophysiology of endothelial cells; molecular and cellular biology; inflammatory cytokines; osteogenic differentiation

Special Issue Information

Dear Colleagues,

Magnesium (Mg) is essential for life and health, since it is implicated in every primary metabolic and biochemical process in the cell, including energy metabolism, DNA duplication, RNA transcription, protein synthesis, trans-phosphorylation, and redox reactions. Mg also acts as an intracellular second messenger and is considered a natural calcium antagonist. Not surprisingly, there is no doubt about the compelling role of Mg in the maintenance of cellular homeostasis and in the control of cell proliferation.

Although several studies suggest that extracellular Mg differently affects cell differentiation, a comprehensive survey on this topic is lacking. Intriguing results were recently obtained in embryonic stem cells, since Mg withdrawal and mesendogen, an inhibitor of the channels responsible for cellular Mg import, promote mesoderm and endoderm differentiation. Moreover, Mg deficiency promotes the reprogramming of human mesenchymal stem cells, thus indicating that a proper tuning of Mg homeostasis might be viewed as a novel tool to chemically manipulate stem cell fate.

Mg is also involved also development (i.e. the processes by which multicellular organisms grow and develop). Indeed, gestational Mg deficiency is linked to birth defects in experimental models and also in humans, but the molecular mechanisms have been unveiled only in part.

This Special Issue entitled “Magnesium in Differentiation and Development” aims to provide a research platform for the collection of high-quality up-to-date original and review articles on various aspects of the cellular and molecular biology of Mg involvement in differentiation and development.

Prof. Dr. Stefano Iotti
Prof. Dr. Jeanette A. M. Maier
Guest Editor

Manuscript Submission Information

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Keywords

  • mesenchymal stem cell differentiation
  • cardiac progenitor cell differentiation
  • muscle differentiation
  • immune cell differentiation
  • vascular cell differentiation
  • biomineralization
  • stress-induced cell differentiation
  • terminal differentiation and replicative senescence
  • intracellular magnesium
  • magnesium transporters
  • cell interaction and magnesium-based biomaterials
  • embryonic development
  • gastrulation
  • fertilization

Published Papers (9 papers)

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Editorial

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3 pages, 189 KiB  
Editorial
The Recurring Word in the Scientific Articles about the Role of Mg in Living Systems Is “Key”
by Jeanette A. Maier and Stefano Iotti
Int. J. Mol. Sci. 2023, 24(12), 10100; https://doi.org/10.3390/ijms241210100 - 14 Jun 2023
Viewed by 546
Abstract
Magnesium (Mg) is a versatile element involved in all aspects of life on our planet [...] Full article
(This article belongs to the Special Issue Magnesium in Differentiation and Development)

Research

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14 pages, 3154 KiB  
Article
Analysis of Intracellular Magnesium and Mineral Depositions during Osteogenic Commitment of 3D Cultured Saos2 Cells
by Giovanna Picone, Concettina Cappadone, Alice Pasini, Joseph Lovecchio, Marilisa Cortesi, Giovanna Farruggia, Marco Lombardo, Alessandra Gianoncelli, Lucia Mancini, Menk Ralf H., Sandro Donato, Emanuele Giordano, Emil Malucelli and Stefano Iotti
Int. J. Mol. Sci. 2020, 21(7), 2368; https://doi.org/10.3390/ijms21072368 - 30 Mar 2020
Cited by 17 | Viewed by 3286
Abstract
In this study, we explore the behaviour of intracellular magnesium during bone phenotype modulation in a 3D cell model built to mimic osteogenesis. In addition, we measured the amount of magnesium in the mineral depositions generated during osteogenic induction. A two-fold increase of [...] Read more.
In this study, we explore the behaviour of intracellular magnesium during bone phenotype modulation in a 3D cell model built to mimic osteogenesis. In addition, we measured the amount of magnesium in the mineral depositions generated during osteogenic induction. A two-fold increase of intracellular magnesium content was found, both at three and seven days from the induction of differentiation. By X-ray microscopy, we characterized the morphology and chemical composition of the mineral depositions secreted by 3D cultured differentiated cells finding a marked co-localization of Mg with P at seven days of differentiation. This is the first experimental evidence on the presence of Mg in the mineral depositions generated during biomineralization, suggesting that Mg incorporation occurs during the bone forming process. In conclusion, this study on the one hand attests to an evident involvement of Mg in the process of cell differentiation, and, on the other hand, indicates that its multifaceted role needs further investigation. Full article
(This article belongs to the Special Issue Magnesium in Differentiation and Development)
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18 pages, 2382 KiB  
Article
SNPs rs11240569, rs708727, and rs823156 in SLC41A1 Do Not Discriminate Between Slovak Patients with Idiopathic Parkinson’s Disease and Healthy Controls: Statistics and Machine-Learning Evidence
by Michal Cibulka, Maria Brodnanova, Marian Grendar, Milan Grofik, Egon Kurca, Ivana Pilchova, Oto Osina, Zuzana Tatarkova, Dusan Dobrota and Martin Kolisek
Int. J. Mol. Sci. 2019, 20(19), 4688; https://doi.org/10.3390/ijms20194688 - 21 Sep 2019
Cited by 7 | Viewed by 3181
Abstract
Gene SLC41A1 (A1) is localized within Parkinson’s disease-(PD)-susceptibility locus PARK16 and encodes for the Na+/Mg2+-exchanger. The association of several A1 SNPs with PD has been studied. Two, rs11240569 and rs823156, have been associated with reduced PD-susceptibility primarily [...] Read more.
Gene SLC41A1 (A1) is localized within Parkinson’s disease-(PD)-susceptibility locus PARK16 and encodes for the Na+/Mg2+-exchanger. The association of several A1 SNPs with PD has been studied. Two, rs11240569 and rs823156, have been associated with reduced PD-susceptibility primarily in Asian populations. Here, we examined the association of rs11240569, rs708727, and rs823156 with PD in the Slovak population and their power to discriminate between PD patients and healthy controls. The study included 150 PD patients and 120 controls. Genotyping was performed with the TaqMan® approach. Data were analyzed by conventional statistics and Random Forest machine-learning (ML) algorithm. Individually, none of the three SNPs is associated with an altered risk for PD-onset in Slovaks. However, a combination of genotypes of SNP-triplet GG(rs11240569)/AG(rs708727)/AA(rs823156) is significantly (p < 0.05) more frequent in the PD (13.3%) than in the control (5%) cohort. ML identified the power of the tested SNPs in isolation or of their singlets (joined), duplets and triplets to discriminate between PD-patients and healthy controls as zero. Our data further substantiate differences between diverse populations regarding the association of A1 polymorphisms with PD-susceptibility. Lack of power of the tested SNPs to discriminate between PD and healthy cases render their clinical/diagnostic relevance in the Slovak population negligible. Full article
(This article belongs to the Special Issue Magnesium in Differentiation and Development)
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19 pages, 3336 KiB  
Article
Magnesium Sulfate Mitigates the Progression of Monocrotaline Pulmonary Hypertension in Rats
by Chao-Yuan Chang, Hung-Jen Shih, I-Tao Huang, Pei-Shan Tsai, Kung-Yen Chen and Chun-Jen Huang
Int. J. Mol. Sci. 2019, 20(18), 4622; https://doi.org/10.3390/ijms20184622 - 18 Sep 2019
Cited by 16 | Viewed by 3654
Abstract
We investigated whether magnesium sulfate (MgSO4) mitigated pulmonary hypertension progression in rats. Pulmonary hypertension was induced by a single intraperitoneal injection of monocrotaline (60 mg/kg). MgSO4 (100 mg/kg) was intraperitoneally administered daily for 3 weeks, from the seventh day after [...] Read more.
We investigated whether magnesium sulfate (MgSO4) mitigated pulmonary hypertension progression in rats. Pulmonary hypertension was induced by a single intraperitoneal injection of monocrotaline (60 mg/kg). MgSO4 (100 mg/kg) was intraperitoneally administered daily for 3 weeks, from the seventh day after monocrotaline injection. Adult male rats were randomized into monocrotaline (MCT) or monocrotaline plus MgSO4 (MM) groups (n = 15 per group); control groups were maintained simultaneously. For analysis, surviving rats were euthanized on the 28th day after receiving monocrotaline. The survival rate was higher in the MM group than in the MCT group (100% versus 73.3%, p = 0.043). Levels of pulmonary artery wall thickening, α-smooth muscle actin upregulation, right ventricular systolic pressure increase, and right ventricular hypertrophy were lower in the MM group than in the MCT group (all p < 0.05). Levels of lipid peroxidation, mitochondrial injury, inflammasomes and cytokine upregulation, and apoptosis in the lungs and right ventricle were lower in the MM group than in the MCT group (all p < 0.05). Notably, the mitigation effects of MgSO4 on pulmonary artery wall thickening and right ventricular hypertrophy were counteracted by exogenous calcium chloride. In conclusion, MgSO4 mitigates pulmonary hypertension progression, possibly by antagonizing calcium. Full article
(This article belongs to the Special Issue Magnesium in Differentiation and Development)
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17 pages, 2989 KiB  
Article
Magnesium Is a Key Regulator of the Balance between Osteoclast and Osteoblast Differentiation in the Presence of Vitamin D3
by Fabiana Mammoli, Sara Castiglioni, Sandra Parenti, Concettina Cappadone, Giovanna Farruggia, Stefano Iotti, Pierpaola Davalli, Jeanette A.M. Maier, Alexis Grande and Chiara Frassineti
Int. J. Mol. Sci. 2019, 20(2), 385; https://doi.org/10.3390/ijms20020385 - 17 Jan 2019
Cited by 61 | Viewed by 5856
Abstract
Magnesium (Mg) is crucial for bone health. Low concentrations of Mg inhibit the activity of osteoblasts while promoting that of osteoclasts, with the final result of inducing osteopenia. Conversely, little is known about the effects of high concentrations of extracellular Mg on osteoclasts [...] Read more.
Magnesium (Mg) is crucial for bone health. Low concentrations of Mg inhibit the activity of osteoblasts while promoting that of osteoclasts, with the final result of inducing osteopenia. Conversely, little is known about the effects of high concentrations of extracellular Mg on osteoclasts and osteoblasts. Since the differentiation and activation of these cells is coordinated by vitamin D3 (VD3), we investigated the effects of high extracellular Mg, as well as its impact on VD3 activity, in these cells. U937 cells were induced to osteoclastic differentiation by VD3 in the presence of supra-physiological concentrations (>1 mM) of extracellular Mg. The effect of high Mg concentrations was also studied in human bone-marrow-derived mesenchymal stem cells (bMSCs) induced to differentiate into osteoblasts by VD3. We demonstrate that high extra-cellular Mg levels potentiate VD3-induced osteoclastic differentiation, while decreasing osteoblastogenesis. We hypothesize that Mg might reprogram VD3 activity on bone remodeling, causing an unbalanced activation of osteoclasts and osteoblasts. Full article
(This article belongs to the Special Issue Magnesium in Differentiation and Development)
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Review

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15 pages, 1519 KiB  
Review
New Aspects of Magnesium Function: A Key Regulator in Nucleosome Self-Assembly, Chromatin Folding and Phase Separation
by Takashi Ohyama
Int. J. Mol. Sci. 2019, 20(17), 4232; https://doi.org/10.3390/ijms20174232 - 29 Aug 2019
Cited by 23 | Viewed by 4743
Abstract
Metal cations are associated with many biological processes. The effects of these cations on nucleic acids and chromatin were extensively studied in the early stages of nucleic acid and chromatin research. The results revealed that some monovalent and divalent metal cations, including Mg [...] Read more.
Metal cations are associated with many biological processes. The effects of these cations on nucleic acids and chromatin were extensively studied in the early stages of nucleic acid and chromatin research. The results revealed that some monovalent and divalent metal cations, including Mg2+, profoundly affect the conformations and stabilities of nucleic acids, the folding of chromatin fibers, and the extent of chromosome condensation. Apart from these effects, there have only been a few reports on the functions of these cations. In 2007 and 2013, however, Mg2+-implicated novel phenomena were found: Mg2+ facilitates or enables both self-assembly of identical double-stranded (ds) DNA molecules and self-assembly of identical nucleosomes in vitro. These phenomena may be deeply implicated in the heterochromatin domain formation and chromatin-based phase separation. Furthermore, a recent study showed that elevation of the intranuclear Mg2+ concentration causes unusual differentiation of mouse ES (embryonic stem) cells. All of these phenomena seem to be closely related to one another. Mg2+ seems to be a key regulator of chromatin dynamics and chromatin-based biological processes. Full article
(This article belongs to the Special Issue Magnesium in Differentiation and Development)
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26 pages, 3558 KiB  
Review
Magnesium Is a Key Player in Neuronal Maturation and Neuropathology
by Ryu Yamanaka, Yutaka Shindo and Kotaro Oka
Int. J. Mol. Sci. 2019, 20(14), 3439; https://doi.org/10.3390/ijms20143439 - 12 Jul 2019
Cited by 84 | Viewed by 13958
Abstract
Magnesium (Mg) is the second most abundant cation in mammalian cells, and it is essential for numerous cellular processes including enzymatic reactions, ion channel functions, metabolic cycles, cellular signaling, and DNA/RNA stabilities. Because of the versatile and universal nature of Mg2+, [...] Read more.
Magnesium (Mg) is the second most abundant cation in mammalian cells, and it is essential for numerous cellular processes including enzymatic reactions, ion channel functions, metabolic cycles, cellular signaling, and DNA/RNA stabilities. Because of the versatile and universal nature of Mg2+, the homeostasis of intracellular Mg2+ is physiologically linked to growth, proliferation, differentiation, energy metabolism, and death of cells. On the cellular and tissue levels, maintaining Mg2+ within optimal levels according to the biological context, such as cell types, developmental stages, extracellular environments, and pathophysiological conditions, is crucial for development, normal functions, and diseases. Hence, Mg2+ is pathologically involved in cancers, diabetes, and neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease, and demyelination. In the research field regarding the roles and mechanisms of Mg2+ regulation, numerous controversies caused by its versatility and complexity still exist. As Mg2+, at least, plays critical roles in neuronal development, healthy normal functions, and diseases, appropriate Mg2+ supplementation exhibits neurotrophic effects in a majority of cases. Hence, the control of Mg2+ homeostasis can be a candidate for therapeutic targets in neuronal diseases. In this review, recent results regarding the roles of intracellular Mg2+ and its regulatory system in determining the cell phenotype, fate, and diseases in the nervous system are summarized, and an overview of the comprehensive roles of Mg2+ is provided. Full article
(This article belongs to the Special Issue Magnesium in Differentiation and Development)
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14 pages, 631 KiB  
Review
Magnesium and Drugs
by Uwe Gröber
Int. J. Mol. Sci. 2019, 20(9), 2094; https://doi.org/10.3390/ijms20092094 - 28 Apr 2019
Cited by 56 | Viewed by 11176
Abstract
Several drugs including diuretics and proton-pump inhibitors can cause magnesium loss and hypomagnesemia. Magnesium and drugs use the same transport and metabolism pathways in the body for their intestinal absorption, metabolism, and elimination. This means that when one or more drug is taken, [...] Read more.
Several drugs including diuretics and proton-pump inhibitors can cause magnesium loss and hypomagnesemia. Magnesium and drugs use the same transport and metabolism pathways in the body for their intestinal absorption, metabolism, and elimination. This means that when one or more drug is taken, there is always a potential risk of interaction with the magnesium status. Consequently the action of a drug may be adversely affected by magnesium (e.g., magnesium, calcium, and zinc can interfere with the gastrointestinal absorption of tetracycline antibiotics) and simultaneously the physiological function of minerals such as magnesium may be impaired by a drug (e.g., diuretics induce renal magnesium loss). Given the ever-increasing number of drugs on the market and the frequency with which they are used, greater attention must be paid in daily medical and pharmaceutical practice focused in particular on the adverse effects of drug therapy on magnesium status in order to minimize the potential risk to the health of patients. Full article
(This article belongs to the Special Issue Magnesium in Differentiation and Development)
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19 pages, 2254 KiB  
Review
TRPM7, Magnesium, and Signaling
by Zhi-Guo Zou, Francisco J. Rios, Augusto C. Montezano and Rhian M. Touyz
Int. J. Mol. Sci. 2019, 20(8), 1877; https://doi.org/10.3390/ijms20081877 - 16 Apr 2019
Cited by 96 | Viewed by 11936
Abstract
The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed chanzyme that possesses an ion channel permeable to the divalent cations Mg2+, Ca2+, and Zn2+, and an α-kinase that phosphorylates downstream substrates. TRPM7 and its [...] Read more.
The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed chanzyme that possesses an ion channel permeable to the divalent cations Mg2+, Ca2+, and Zn2+, and an α-kinase that phosphorylates downstream substrates. TRPM7 and its homologue TRPM6 have been implicated in a variety of cellular functions and is critically associated with intracellular signaling, including receptor tyrosine kinase (RTK)-mediated pathways. Emerging evidence indicates that growth factors, such as EGF and VEGF, signal through their RTKs, which regulate activity of TRPM6 and TRPM7. TRPM6 is primarily an epithelial-associated channel, while TRPM7 is more ubiquitous. In this review we focus on TRPM7 and its association with growth factors, RTKs, and downstream kinase signaling. We also highlight how interplay between TRPM7, Mg2+ and signaling kinases influences cell function in physiological and pathological conditions, such as cancer and preeclampsia. Full article
(This article belongs to the Special Issue Magnesium in Differentiation and Development)
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