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Calcium Metabolism and Regulation
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Calcium Metabolism and Regulation

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

Deadline for manuscript submissions: 20 February 2025 | Viewed by 4672

Special Issue Editors

Dr. Hermann Salmhofer

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Guest Editor
Department of Internal Medicine I, Nephrology, University Hospital Salzburg, Müllner Hauptstrasse 48, A-5020 Salzburg, Austria
Interests: nephrocalcinosis; nephrolithiasis; vascular calcification; calciphylaxis; calcifying skin disorders; vitamin D; parathyroid hormone; sodium thiosulfate; CKD-MBD; vitamin K2; myoinositol-hexaphosphate; oxidative stress
Prof. Dr. Michael Lichtenauer

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Guest Editor
Clinic of Internal Medicine II, Department of Cardiology, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria
Interests: apoptosis; clinical cardiology; heart failure; hypertension; cell culture; ELISA; echocardiography; flow cytometry; atrial fibrillation; atherosclerosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Calcium has multiple roles in biology, including cell signaling, motor function, and bone mineralization. Regulation of calcium homeostasis includes maintenance of normal blood levels, bone mineralization and inhibition of extraosseous depositions, neuronal and muscular function, intracellular compartmentation, shifting, and signaling. On a systemic level, this involves complex hormonal regulation of calcium and interconnected phosphate metabolism, prevention of mineral precipitation by a multi-factorial balance between promoters and inhibitors of calcification, and targeted transport mechanisms from soft tissues to bone structures. On a tissue level, local activation of specific proteins and enzymes may influence mineral deposition. On a cellular and subcellular level, it comprises regulation of calcium flux via ion channels and intracellular calcium shifts, as well as interaction with calcium-binding proteins for activation of further proteins and membrane functions. This Special Issue aims to give a scope of new developments in various areas of physiological and pathological calcium metabolism and regulation, including osteogenic transdifferentiation, the formation of pathological mineral depositions, and candidate molecules for the treatment of calcifying disorders.

So we would like to cordially invite you to contribute new scientific discoveries to this fascinating and multi-facetted field of research.

Dr. Hermann Salmhofer
Dr. Michael Lichtenauer
Guest Editors

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Keywords

  • pathologic calcification
  • calcification inhibitors
  • calciprotein particles
  • Runx-2
  • apatite
  • matrix Gla protein
  • fetuin-A
  • vitamin D
  • parathyroid hormone

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Published Papers (3 papers)

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Research

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31 pages, 15032 KiB  
Article
Proteomic Profiling of Endothelial Cell Secretomes After Exposure to Calciprotein Particles Reveals Downregulation of Basement Membrane Assembly and Increased Release of Soluble CD59
by Alexander Stepanov, Daria Shishkova, Victoria Markova, Yulia Markova, Alexey Frolov, Anastasia Lazebnaya, Karina Oshchepkova, Daria Perepletchikova, Daria Smirnova, Liubov Basovich, Egor Repkin and Anton Kutikhin
Int. J. Mol. Sci. 2024, 25(21), 11382; https://doi.org/10.3390/ijms252111382 - 23 Oct 2024
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Abstract
Calciprotein particles (CPPs) are essential circulating scavengers of excessive Ca2+ and PO43− ions, representing a vehicle that removes them from the human body and precludes extraskeletal calcification. Having been internalised by endothelial cells (ECs), CPPs induce their dysfunction, which is [...] Read more.
Calciprotein particles (CPPs) are essential circulating scavengers of excessive Ca2+ and PO43− ions, representing a vehicle that removes them from the human body and precludes extraskeletal calcification. Having been internalised by endothelial cells (ECs), CPPs induce their dysfunction, which is accompanied by a remarkable molecular reconfiguration, although little is known about this process’s extracellular signatures. Here, we applied ultra-high performance liquid chromatography-tandem mass spectrometry to perform a secretome-wide profiling of the cell culture supernatant from primary human coronary artery ECs (HCAECs) and internal thoracic artery ECs (HITAECs) treated with primary CPPs (CPP-P), secondary CPPs (CPP-S), magnesiprotein particles (MPPs), or Ca2+/Mg2+-free Dulbecco’s phosphate-buffered saline (DPBS) for 24 h. Incubation with CPP-P/CPP-S significantly altered the profiles of secreted proteins, delineating physiological and pathological endothelial secretomes. Neither pathway enrichment analysis nor the interrogation of protein–protein interactions detected extracellular matrix- and basement membrane-related molecular terms in the protein datasets from CPP-P/CPP-S-treated ECs. Both proteomic profiling and enzyme-linked immunosorbent assay identified an increased level of protectin (CD59) and reduced levels of osteonectin (SPARC), perlecan (HSPG2), and fibronectin (FN1) in the cell culture supernatant upon CPP-P/CPP-S treatment. Elevated soluble CD59 and decreased release of basement membrane components might be considered as potential signs of dysfunctional endothelium. Full article
(This article belongs to the Special Issue Calcium Metabolism and Regulation)
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Review

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13 pages, 1568 KiB  
Review
Targeting Calcitriol Metabolism in Acute Vitamin D Toxicity—A Comprehensive Review and Clinical Insight
by Simon Aberger, Nikolaus Schreiber, Stefan Pilz, Kathrin Eller, Alexander R. Rosenkranz and Alexander H. Kirsch
Int. J. Mol. Sci. 2024, 25(18), 10003; https://doi.org/10.3390/ijms251810003 - 17 Sep 2024
Cited by 2 | Viewed by 1588
Abstract
High-dose vitamin D supplementation is common in the general population, but unsupervised high-dose supplementation in vitamin D-replete individuals poses a risk of severe toxicity. Susceptibility to vitamin D toxicity shows a significant inter-individual variability that may in part be explained by genetic predispositions [...] Read more.
High-dose vitamin D supplementation is common in the general population, but unsupervised high-dose supplementation in vitamin D-replete individuals poses a risk of severe toxicity. Susceptibility to vitamin D toxicity shows a significant inter-individual variability that may in part be explained by genetic predispositions (i.e., CYP24A1 polymorphism). The classic manifestation of vitamin D toxicity is hypercalcemia, which may be refractory to conventional therapy. Its causes include the endogenous overaction of 1α-hydroxylase, monogenic alterations affecting vitamin D metabolizing enzymes and exogenous vitamin D intoxication. In this manuscript, we include a literature review of potential pharmacological interventions targeting calcitriol metabolism to treat vitamin D intoxication and present a case of severe, exogenous vitamin D intoxication responding to systemic corticosteroids after the failure of conventional therapy. Systemic glucocorticoids alleviate acute hypercalcemia by inhibiting enteric calcium absorption and increasing the degradation of vitamin D metabolites but may cause adverse effects. Inhibitors of 1α-hydroxylase (keto/fluconazole) and inducers of CYP3A4 (rifampicin) may be considered steroid-sparing alternatives for the treatment of vitamin D intoxication. Full article
(This article belongs to the Special Issue Calcium Metabolism and Regulation)
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27 pages, 4834 KiB  
Review
Proteomic Biomarkers Associated with Low Bone Mineral Density: A Systematic Review
by Adriana Becerra-Cervera, Anna D. Argoty-Pantoja, Diana I. Aparicio-Bautista, Priscilla López-Montoya, Berenice Rivera-Paredez, Alberto Hidalgo-Bravo and Rafael Velázquez-Cruz
Int. J. Mol. Sci. 2024, 25(14), 7526; https://doi.org/10.3390/ijms25147526 - 9 Jul 2024
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Abstract
Osteoporosis is a globally relevant public health issue. Our study aimed to summarize the knowledge on the proteomic biomarkers for low bone mineral density over the last years. We conducted a systematic review following the PRISMA guidelines; the scoured databases were PubMed, Web [...] Read more.
Osteoporosis is a globally relevant public health issue. Our study aimed to summarize the knowledge on the proteomic biomarkers for low bone mineral density over the last years. We conducted a systematic review following the PRISMA guidelines; the scoured databases were PubMed, Web of Sciences, Scopus, and EBSCO, from inception to 2 June 2023. A total of 610 relevant studies were identified and 33 were assessed for eligibility. Finally, 29 studies met the criteria for this systematic review. The risk of bias was evaluated using the Joanna Briggs Institute Critical Appraisal Checklist tool. From the studies selected, 154 proteins were associated with changes of bone mineral density, from which only 10 were reported in at least two articles. The protein–protein network analysis indicated potential biomarkers involved in the skeletal system, immune system process, regulation of protein metabolic process, regulation of signaling, transport, cellular component assembly, cell differentiation, hemostasis, and extracellular matrix organization. Mass spectrometry-based proteomic profiling has allowed the discovery of new biomarkers with diagnostic potential. However, it is necessary to compare and validate the potential biomarkers in different populations to determine their association with bone metabolism and evaluate their translation to the clinical management of osteoporosis. Full article
(This article belongs to the Special Issue Calcium Metabolism and Regulation)
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