scholarly journals The Biological Activities of Vitamin D and Its Receptor in Relation to Calcium and Bone Homeostasis, Cancer, Immune and Cardiovascular Systems, Skin Biology, and Oral Health

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
R. A. G. Khammissa ◽  
J. Fourie ◽  
M. H. Motswaledi ◽  
R. Ballyram ◽  
J. Lemmer ◽  
...  
Keyword(s):  
Vitamin D ◽  
Calcium Homeostasis ◽  
Dna Sequences ◽  
Target Genes ◽  
Biological Activities ◽  
Biological Effects ◽  
Active Form ◽  
Vitamin D Supplementation ◽  
Biologically Active ◽  
Bone Homeostasis

Vitamin D plays an important role in calcium homeostasis and bone metabolism, with the capacity to modulate innate and adaptive immune function, cardiovascular function, and proliferation and differentiation of both normal and malignant keratinocytes. 1,25(OH)2D, the biologically active form of vitamin D, exerts most of its functions through the almost universally distributed nuclear vitamin D receptor (VDR). Upon stimulation by 1,25(OH)2D, VDR forms a heterodimer with the retinoid X receptor (RXR). In turn, VDR/RXR binds to DNA sequences termed vitamin D response elements in target genes, regulating gene transcription. In order to exert its biological effects, VDR signalling interacts with other intracellular signalling pathways. In some cases 1,25(OH)2D exerts its biological effects without regulating either gene expression or protein synthesis. Although the regulatory role of vitamin D in many biological processes is well documented, there is not enough evidence to support the therapeutic use of vitamin D supplementation in the prevention or treatment of infectious, immunoinflammatory, or hyperproliferative disorders. In this review we highlight the effects of 1,25(OH)2D on bone and calcium homeostasis, on cancer, and refer to its effects on the cardiovascular and immune systems.

scholarly journals Key Vitamin D Target Genes with Functions in the Immune System

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1140 ◽  
Author(s):  
Oona Koivisto ◽  
Andrea Hanel ◽  
Carsten Carlberg
Keyword(s):  
Vitamin D ◽  
Adaptive Immunity ◽  
Vitamin D3 ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Active Form ◽  
Biologically Active ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Innate And Adaptive Immunity

The biologically active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), modulates innate and adaptive immunity via genes regulated by the transcription factor vitamin D receptor (VDR). In order to identify the key vitamin D target genes involved in these processes, transcriptome-wide datasets were compared, which were obtained from a human monocytic cell line (THP-1) and peripheral blood mononuclear cells (PBMCs) treated in vitro by 1,25(OH)2D3, filtered using different approaches, as well as from PBMCs of individuals supplemented with a vitamin D3 bolus. The led to the genes ACVRL1, CAMP, CD14, CD93, CEBPB, FN1, MAPK13, NINJ1, LILRB4, LRRC25, SEMA6B, SRGN, THBD, THEMIS2 and TREM1. Public epigenome- and transcriptome-wide data from THP-1 cells were used to characterize these genes based on the level of their VDR-driven enhancers as well as the level of the dynamics of their mRNA production. Both types of datasets allowed the categorization of the vitamin D target genes into three groups according to their role in (i) acute response to infection, (ii) infection in general and (iii) autoimmunity. In conclusion, 15 genes were identified as major mediators of the action of vitamin D in innate and adaptive immunity and their individual functions are explained based on different gene regulatory scenarios.

scholarly journals Vitamin D Deficiency as It Relates to Oral Immunity and Chronic Periodontitis

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
R. A. G. Khammissa ◽  
R. Ballyram ◽  
Y. Jadwat ◽  
J. Fourie ◽  
J. Lemmer ◽  
...  
Keyword(s):  
Vitamin D ◽  
Serum Level ◽  
Chronic Periodontitis ◽  
Active Form ◽  
Antibacterial Properties ◽  
Vitamin D Supplementation ◽  
Biologically Active ◽  
Periodontal Treatment ◽  
Periodontal Health ◽  
Cross Sectional

The biologically active form of vitamin D, 1,25 dihydroxyvitamin D (1,25(OH)2D) and its receptor, the vitamin D receptor (VDR), play roles in maintaining oral immunity and the integrity of the periodontium. Results of observational cross-sectional clinical studies investigating the association between vitamin D serum level and the incidence and severity of chronic periodontitis indicate that, perhaps owing to the immunomodulatory, anti-inflammatory, and antibacterial properties of 1,25(OH)2D/VDR signalling, a sufficient serum level of vitamin D is necessary for the maintenance of periodontal health. In cases of established chronic periodontitis, vitamin D supplementation is associated with reduction in the severity of periodontitis. As cross-sectional studies provide only weak evidence for any causal association and therefore are of questionable value, either longitudinal cohort studies, case controlled studies, or randomized control trials are needed to determine whether or not deficiency of vitamin D is a risk factor for chronic periodontitis, and whether or not vitamin D supplementation adjunctive to standard periodontal treatment is in any way beneficial. In this article, we discuss the relationship between vitamin D, oral immunity and periodontal disease and review the rationale for using vitamin D supplementation to help maintain periodontal health and as an adjunct to standard periodontal treatment.

scholarly journals Vitamin D and Lumisterol Hydroxyderivatives Can Act on Liver X Receptors (LXRs)

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A820-A820
Author(s):  
Andrzej Slominski ◽  
Tae-Kang Kim ◽  
Shariq Qayyum ◽  
Yuwei Song ◽  
Zorica Janjetovic ◽  
...  
Keyword(s):  
Vitamin D ◽  
Target Genes ◽  
Active Form ◽  
Human Keratinocytes ◽  
Major Product ◽  
Dermal Fibroblasts ◽  
Biologically Active ◽  
Liver X Receptors ◽  
X Receptors ◽  
Dynamics Simulations

Abstract New pathways of vitamin D3 (D3) activation initiated by CYP11A1 and involving other CYPs have been discovered. At least 15 hydroxyderivatives, including 20(OH)D3 as the major product, are generated by these pathways (1,2) with some being present in human serum, epidermis, and pig adrenals. CYP11A1 can also metabolize 7-dehydrocholesterol to produce 7-dehydropregnenolone, which can be further modified by steroidogenic enzymes generating Δ7-steroids (1,2). Lastly, CYP11A1 and CYP27A1 act on lumisterol (L3) producing at least 9 biologically active derivatives (1,2). Thus, new pathways generating a large number of biologically active secosteroids and lumisterol-derivatives have now been described. These compounds interact with the vitamin D receptor (VDR), retinoic acid receptors (RORs) α and γ, and the aryl hydrocarbon receptor (AhR)(1). These findings challenge dogmas that lumisterol is biologically inactive and that 1,25(OH)2D3 is the only active form of D3 exerting its effects exclusively through interaction with the VDR. In view of the above and since liver X receptors (LXRs) can be activated by oxysterols, we investigated the interactions of novel products of L3 and D3 metabolism with LXRs. Molecular docking, using crystal structures of the ligand binding domains (LBDs) of LXRα and β, revealed high docking scores for L3 and D3 hydroxymetabolites, like those of the natural ligands, predicting good receptor binding. RNA sequencing of murine dermal fibroblasts stimulated with D3-hydroxyderivatives revealed LXR as the second major nuclear receptor signaling pathway for several D3-hydroxyderivatives, including 1,25(OH)2D3. The involvement of LXRs was validated by the induction of several genes downstream of LXR. Furthermore, L3 and D3-hydroxyderivatives activated an LXR-response element (LXRE)-driven reporter in CHO cells and human keratinocytes. For keratinocytes, enhanced expression of LXR target genes was also observed supporting the involvement of LXR. Importantly, L3 and D3 derivatives showed high affinity binding to the LBD of the LXRα and β in LanthaScreen TR-FRET LXRα and β coactivator assays. The majority of metabolites functioned as LXRα/β agonists; however, 1,20,25(OH)3D3, 1,25(OH)2D3, 1,20(OH)2D3 and 25(OH)D3 acted as inverse agonists of LXRα, but as agonists of LXRβ. Molecular dynamics simulations performed for selected compounds, including 1,25(OH)2D3, 1,20(OH)2D3, 25(OH)D3, 20(OH)D3, 20(OH)L3 and 20,22(OH)2L3, showed overlapping and different interactions with LXRs. Identification of D3 and L3 derivatives as ligands for LXRs changes the accepted paradigms on their biological role and mechanism of action. 1. Cell Biochem Biophys. 2020;78(2):165-180. 2. J Steroid Biochem Mol Biol. 2019;186:4-21.

scholarly journals Common and personal target genes of the micronutrient vitamin D in primary immune cells from human peripheral blood

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Andrea Hanel ◽  
Antonio Neme ◽  
Marjo Malinen ◽  
Emmi Hämäläinen ◽  
Henna-Riikka Malmberg ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immune System ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Active Form ◽  
Biologically Active ◽  
Expression Change

AbstractVitamin D is essential for the function of the immune system. In this study, we treated peripheral blood mononuclear cells (PBMCs) of healthy adults with the biologically active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) using two different approaches: single repeats with PBMCs obtained from a cohort of 12 individuals and personalized analysis based on triplicates of five study participants. This identified 877 (cohort approach) and 3951 (personalized approach) genes that significantly (p < 0.05) changed their expression 24 h after 1,25(OH)2D3 stimulation. From these, 333 and 1232 were classified as supertargets, a third of which were identified as novel. Individuals differed largely in their vitamin D response not only by the magnitude of expression change but also by their personal selection of (super)target genes. Functional analysis of the target genes suggested the overarching role of vitamin D in the regulation of metabolism, proliferation and differentiation, but in particular in the control of functions mediated by the innate and adaptive immune system, such as responses to infectious diseases and chronic inflammatory disorders. In conclusion, immune cells are an important target of vitamin D and common genes may serve as biomarkers for personal responses to the micronutrient.

scholarly journals A hierarchical regulatory network analysis of the vitamin D induced transcriptome reveals novel regulators and complete VDR dependency in monocytes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Timothy Warwick ◽  
Marcel H. Schulz ◽  
Stefan Günther ◽  
Ralf Gilsbach ◽  
Antonio Neme ◽  
...  
Keyword(s):  
Vitamin D ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Target Genes ◽  
Active Form ◽  
Transcriptional Response ◽  
Biologically Active ◽  
Open Chromatin ◽  
Monocytic Cell ◽  
Monocytic Cell Line

AbstractThe transcription factor vitamin D receptor (VDR) is the high affinity nuclear target of the biologically active form of vitamin D3 (1,25(OH)2D3). In order to identify pure genomic transcriptional effects of 1,25(OH)2D3, we used VDR cistrome, transcriptome and open chromatin data, obtained from the human monocytic cell line THP-1, for a novel hierarchical analysis applying three bioinformatics approaches. We predicted 75.6% of all early 1,25(OH)2D3-responding (2.5 or 4 h) and 57.4% of the late differentially expressed genes (24 h) to be primary VDR target genes. VDR knockout led to a complete loss of 1,25(OH)2D3–induced genome-wide gene regulation. Thus, there was no indication of any VDR-independent non-genomic actions of 1,25(OH)2D3 modulating its transcriptional response. Among the predicted primary VDR target genes, 47 were coding for transcription factors and thus may mediate secondary 1,25(OH)2D3 responses. CEBPA and ETS1 ChIP-seq data and RNA-seq following CEBPA knockdown were used to validate the predicted regulation of secondary vitamin D target genes by both transcription factors. In conclusion, a directional network containing 47 partly novel primary VDR target transcription factors describes secondary responses in a highly complex vitamin D signaling cascade. The central transcription factor VDR is indispensable for all transcriptome-wide effects of the nuclear hormone.

scholarly journals Vitamin D and allergies

2013 ◽  
Vol 78 (3) ◽  
pp. 353-363
Author(s):  
Guro Gafvelin
Keyword(s):  
Vitamin D ◽  
Active Form ◽  
Treatment Strategies ◽  
Risk Groups ◽  
Serum Levels ◽  
Protective Role ◽  
Vitamin D Supplementation ◽  
Biologically Active ◽  
Allergen Specific Immunotherapy

An increasing amount of evidence has established that the biologically active form of vitamin D, 1,25-dihydroxy vitamin D3, possesses immunoregulatory properties. Vitamin D exerts its effects through binding to the nuclear vitamin D receptor (VDR), which is expressed by cells of the immune system. Most of the immunological effects mediated by vitamin D-VDR are regulatory, inhibiting adaptive immune responses. It has become apparent that the incidence of vitamin D insufficiency is surprisingly high in the general population. A link between low vitamin D serum levels and the increased prevalence of allergic diseases has been proposed. This possible connection has been investigated in numerous studies on associations between vitamin D serum concentrations and different allergic conditions, as well as studies on the effect of vitamin D supplementation. Although there is some evidence for a protective role of vitamin D in asthma, no consensus on the role of vitamin D in allergic disease has yet been reached. Still, treatment strategies involving vitamin D supplementation to risk groups, combinatorial corticosteroid and vitamin D treatment in asthma and vitamin D as an immunomodulator in allergen specific immunotherapy show promise for the future.

scholarly journals The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 563
Author(s):  
Jon Vincze ◽  
Brian W. Skinner ◽  
Katherine A. Tucker ◽  
Kory A. Conaway ◽  
Jonathan W. Lowery ◽  
...  
Keyword(s):  
Vitamin D ◽  
Biological Effects ◽  
Fibroblast Growth Factor 23 ◽  
Elevated Serum ◽  
Fractional Excretion ◽  
The United States ◽  
Vitamin D Supplementation ◽  
Loss Of Function ◽  
Case Presentation ◽  
Serum Inorganic Phosphate

The authors present a stereotypical case presentation of X-linked hypophosphatemia (XLH) and provide a review of the pathophysiology and related pharmacology of this condition, primarily focusing on the FDA-approved medication burosumab. XLH is a renal phosphate wasting disorder caused by loss of function mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). Typical biochemical findings include elevated serum levels of bioactive/intact fibroblast growth factor 23 (FGF23) which lead to (i) low serum phosphate levels, (ii) increased fractional excretion of phosphate, and (iii) inappropriately low or normal 1,25-dihydroxyvitamin D (1,25-vitD). XLH is the most common form of heritable rickets and short stature in patients with XLH is due to chronic hypophosphatemia. Additionally, patients with XLH experience joint pain and osteoarthritis from skeletal deformities, fractures, enthesopathy, spinal stenosis, and hearing loss. Historically, treatment for XLH was limited to oral phosphate supplementation, active vitamin D supplementation, and surgical intervention for cases of severe bowed legs. In 2018, the United States Food and Drug Administration (FDA) approved burosumab for the treatment of XLH and this medication has demonstrated substantial benefit compared with conventional therapy. Burosumab binds circulating intact FGF23 and blocks its biological effects in target tissues, resulting in increased serum inorganic phosphate (Pi) concentrations and increased conversion of inactive vitamin D to active 1,25-vitD.

Vitamin D and sleep duration: Is there a bidirectional relationship?

2020 ◽  
Vol 41 (4) ◽  
Author(s):  
Maryam Mosavat ◽  
Aisling Smyth ◽  
Diana Arabiat ◽  
Lisa Whitehead
Keyword(s):  
Vitamin D ◽  
Sleep Duration ◽  
Vitamin D Supplementation ◽  
The Body ◽  
Bone Homeostasis ◽  
Limited Information ◽  
Physiological Processes ◽  
Vitamin D Levels ◽  
Bidirectional Relationship ◽  
Sleep Length

AbstractVitamin D contributes to numerous physiological processes within the body but primarily calcium and bone homeostasis. Emerging evidence highlights a novel role for vitamin D in maintaining and regulating optimal sleep. Sleep is a known regulator of bone health, highlighting the interconnectedness between vitamin D concentrations, sleep duration and bone metabolism. It is possible that the relationship between sleep length and vitamin D is bidirectional, with vitamin D playing a role in sleep health and conversely, sleep affecting vitamin D levels. Nevertheless, limited information on the direction of the interaction is available, and much remains to be learned concerning the complex relationship between insufficient sleep duration and vitamin D deficiency. Given the potential to implement interventions to improve sleep and vitamin D supplementation, understanding this relationship further could represent a novel way to support and improve health.

scholarly journals THE ROLE OF VITAMIN D SUPPLEMENTATION FOR HEAD AND NECK CANCER : A LITERATURE REVIEW

2019 ◽  
Vol 6 (1) ◽  
pp. 59
Author(s):  
Dewi Kania Intan Permatasari ◽  
Irna Sufiawati
Keyword(s):  
Quality Of Life ◽  
Vitamin D ◽  
Head And Neck Cancer ◽  
Literature Review ◽  
Head And Neck ◽  
Vitamin D Deficiency ◽  
Neck Cancer ◽  
Active Form ◽  
Vitamin D Supplementation

Background: Vitamin D has several roles, namely physiological function of calcium and bone metabolism, cell growth and differentiation, immune and cardiovascular function. Vitamin D deficiency can cause the risk of cancer. Head and neck cancer is one of the cancers that occur due to vitamin D deficiency in the body. This literature review was to asses and evaluate the impact and benefits of vitamin D supplementation for head and neck cancer.Discussion: A study found an association between vitamin D supplementation and a low risk of recurrence in conditions of high total vitamin D levels. Another study found a significant increase in quality of life (QOL). The primary mechanism of vitamin D action is mediated through binding of either 1,25(OH)2D3 (active form) or 25(OH)D (less active form) to the VDR, which is a member of the nuclear receptor superfamily of steroid and thyroid hormones with gene-regulatory and consequent anti-proliferative properties.Conclusions: Vitamin D supplementation provides a role in improving the condition of patients with head and neck cancer. Both in terms of suppressing recurrence and in terms of increasing quality of life

scholarly journals Potential Beneficial Effects of Vitamin D in Coronary Artery Disease

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 99 ◽  
Author(s):  
Christian Legarth ◽  
Daniela Grimm ◽  
Marcus Krüger ◽  
Manfred Infanger ◽  
Markus Wehland
Keyword(s):  
Coronary Artery Disease ◽  
Vitamin D ◽  
Coronary Artery ◽  
Vitamin D Supplementation ◽  
Diabetic Patients ◽  
Inverse Association ◽  
Bone Homeostasis ◽  
Beneficial Effects ◽  
Vitamin D Levels ◽  
Artery Disease

Vitamin D plays a pivotal role in bone homeostasis and calcium metabolism. However, recent research has indicated additional beneficial effects of vitamin D on the cardiovascular system. This review aims to elucidate if vitamin D can be used as an add-on treatment in coronary artery disease (CAD). Large-scale epidemiological studies have found a significant inverse association between serum 25(OH)-vitamin D levels and the prevalence of essential hypertension. Likewise, epidemiological data have suggested plasma levels of vitamin D to be inversely correlated to cardiac injury after acute myocardial infarction (MI). Remarkably, in vitro trials have showed that vitamin D can actively suppress the intracellular NF-κB pathway to decrease CAD progression. This is suggested as a mechanistic link to explain how vitamin D may decrease vascular inflammation and atherosclerosis. A review of randomized controlled trials with vitamin D supplementation showed ambiguous results. This may partly be explained by heterogeneous study groups. It is suggested that subgroups of diabetic patients may benefit more from vitamin D supplementation. Moreover, some studies have indicated that calcitriol rather than cholecalciferol exerts more potent beneficial effects on atherosclerosis and CAD. Therefore, further studies are required to clarify these assumptions.

Sign in / Sign up

Export Citation Format

Share Document