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Article ; Online: Vitamin D: A Critical Regulator of Intestinal Physiology.

Christakos, Sylvia

JBMR plus

2021 Volume 5, Issue 12, Page(s) e10554

Abstract: Calcium is required for the functioning of numerous biological processes and is essential for skeletal health. The major source of new calcium is from the diet. The central role of vitamin D in the maintenance of calcium homeostasis is to increase the ... ...

Abstract	Calcium is required for the functioning of numerous biological processes and is essential for skeletal health. The major source of new calcium is from the diet. The central role of vitamin D in the maintenance of calcium homeostasis is to increase the absorption of ingested calcium from the intestine. The critical importance of vitamin D in this process is noted in the causal link between vitamin D deficiency and rickets, as well as in studies using genetically modified mice including mice deficient in the vitamin D receptor (
Language	English
Publishing date	2021-10-06
Publishing country	England
Document type	Journal Article ; Review
ISSN	2473-4039
ISSN (online)	2473-4039
DOI	10.1002/jbm4.10554
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Article: Relationship of the bone phenotype of the Klotho mutant mouse model of accelerated aging to changes in skeletal architecture that occur with chronological aging.

Verlinden, Lieve / Li, Shanshan / Veldurthy, Vaishali / Carmeliet, Geert / Christakos, Sylvia

Frontiers in endocrinology

2024 Volume 15, Page(s) 1310466

Abstract: Introduction: Due to the relatively long life span of rodent models, in order to expediate the identification of novel therapeutics of age related diseases, mouse models of accelerated aging have been developed. In this study we examined skeletal ... ...

Abstract	Introduction: Due to the relatively long life span of rodent models, in order to expediate the identification of novel therapeutics of age related diseases, mouse models of accelerated aging have been developed. In this study we examined skeletal changes in the male and female Methods: 2, 6 and 20-23 month old C57BL/6 mice were obtained from the National Institute of Aging aged rodent colony and wildtype and Results and discussion: Trabecular bone volume (BV/TV) and trabecular number decreased continuously with age in males and females. In contrast to aging mice, an increase in trabecular bone volume and trabecular number was observed in both male and female
MeSH term(s)	Animals ; Female ; Male ; Mice ; Aging/genetics ; Calcium ; Glucuronidase/genetics ; Glucuronidase/metabolism ; Mice, Inbred C57BL ; Phenotype ; Phosphates ; X-Ray Microtomography
Chemical Substances	Calcium (SY7Q814VUP) ; Glucuronidase (EC 3.2.1.31) ; Phosphates ; Kl protein, mouse (EC 3.2.1.31)
Language	English
Publishing date	2024-01-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2024.1310466
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Article ; Online: In search of regulatory circuits that control the biological activity of vitamin D.

Christakos, Sylvia

The Journal of biological chemistry

2017 Volume 292, Issue 42, Page(s) 17559–17560

Abstract: Although the cytochrome P450 CYP27B1 plays a critical role in vitamin D biology, the molecular mechanisms involved in regulation of CYP27B1 have remained undefined. A new study has identified a kidney-specific control module distal to ... ...

Abstract	Although the cytochrome P450 CYP27B1 plays a critical role in vitamin D biology, the molecular mechanisms involved in regulation of CYP27B1 have remained undefined. A new study has identified a kidney-specific control module distal to the
MeSH term(s)	25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics ; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/metabolism ; Animals ; Humans ; Kidney/metabolism ; Multiple Sclerosis/genetics ; Multiple Sclerosis/metabolism ; Vitamin D/genetics ; Vitamin D/metabolism
Chemical Substances	Vitamin D (1406-16-2) ; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase (EC 1.14.15.18) ; CYP27B1 protein, human (EC 1.14.15.18)
Language	English
Publishing date	2017-10-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.H117.806901
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Article ; Online: Role of Coactivator Associated Arginine Methyltransferase 1 (CARM1) in the Regulation of the Biological Function of 1,25-Dihydroxyvitamin D

Mady, Leila J / Zhong, Yan / Dhawan, Puneet / Christakos, Sylvia

Cells

2023 Volume 12, Issue 10

Abstract: 1,25-Dihydroxyvitamin D3 (1,25(OH) ...

Abstract	1,25-Dihydroxyvitamin D3 (1,25(OH)
MeSH term(s)	Animals ; Mice ; Calcitriol/metabolism ; Vitamin D/metabolism ; Vitamin D3 24-Hydroxylase/metabolism ; Protein-Arginine N-Methyltransferases/metabolism
Chemical Substances	1,25-dihydroxyvitamin D (66772-14-3) ; Calcitriol (FXC9231JVH) ; coactivator-associated arginine methyltransferase 1 (EC 2.1.1.319) ; Vitamin D (1406-16-2) ; Vitamin D3 24-Hydroxylase (EC 1.14.15.16) ; Protein-Arginine N-Methyltransferases (EC 2.1.1.319)
Language	English
Publishing date	2023-05-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12101407
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Article ; Online: Intestinal Vitamin D Receptor Is Dispensable for Maintaining Adult Bone Mass in Mice With Adequate Calcium Intake.

Jiang, Heng / Chanpaisaeng, Krittikan / Christakos, Sylvia / Fleet, James C

Endocrinology

2023 Volume 164, Issue 5

Abstract: 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3)-mediated intestinal calcium (Ca) absorption supplies Ca for proper bone mineralization during growth. We tested whether vitamin D receptor (VDR)-mediated 1,25(OH)2D3 signaling is critical for adult Ca absorption and ...

Abstract	1,25-Dihydroxyvitamin D3 (1,25(OH)2D3)-mediated intestinal calcium (Ca) absorption supplies Ca for proper bone mineralization during growth. We tested whether vitamin D receptor (VDR)-mediated 1,25(OH)2D3 signaling is critical for adult Ca absorption and bone by using mice with inducible Vdr gene knockout in the whole intestine (villin-CreERT2+/- × Vdrf/f, WIK) or in the large intestine (Cdx2-CreERT2+/- ×Vdrf/f, LIK). At 4-month-old, Vdr alleles were recombined (0.05 mg tamoxifen/g BW, intraperitoneally [i.p.], 5 days) and mice were fed diets with either 0.5% (adequate) or 0.2% (low) Ca. Ca absorption was examined after 2 weeks while serum 1,25(OH)2D3, bone mass, and bone microarchitecture were examined after 16 weeks. Intestinal and renal gene expression was measured at both time points (n = 12/genotype/diet/time point). On the 0.5% Ca diet, all phenotypes in WIK and LIK mice were similar to the controls. Control mice adapted to the 0.2% low-Ca diet by increasing renal Cyp27b1 mRNA (3-fold), serum 1,25(OH)2D3 level (1.9-fold), and Ca absorption in the duodenum (Dd, + 131%) and proximal colon (PCo, + 28.9%), which prevented bone loss. In WIK mice, low-Ca diet increased serum 1,25(OH)2D3 (4.4-fold) but Ca absorption remained unaltered in the Dd and PCo. Consequently, significant bone loss occurred in WIK mice (e.g., cortical thickness, Ct.Th, -33.7%). LIK mice adapted to the low-Ca diet in the Dd but not the PCo, and the effect on bone phenotypes was milder (e.g., Ct.Th, -13.1%). Our data suggest intestinal VDR in adult mice prevents bone loss under low Ca intake but is dispensable under adequate calcium intake.
MeSH term(s)	Animals ; Mice ; Calcitriol ; Calcium/metabolism ; Intestinal Absorption ; Intestines ; Kidney/metabolism ; Receptors, Calcitriol/genetics ; Receptors, Calcitriol/metabolism ; Vitamin D/metabolism
Chemical Substances	Calcitriol (FXC9231JVH) ; Calcium (SY7Q814VUP) ; Receptors, Calcitriol ; Vitamin D (1406-16-2) ; Vdr protein, mouse
Language	English
Publishing date	2023-03-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/endocr/bqad051
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Article ; Online: New aspects of vitamin D metabolism and action - addressing the skin as source and target.

Bikle, Daniel / Christakos, Sylvia

Nature reviews. Endocrinology

2020 Volume 16, Issue 4, Page(s) 234–252

Abstract: Vitamin D has a key role in stimulating calcium absorption from the gut and promoting skeletal health, as well as many other important physiological functions. Vitamin D is produced in the skin. It is subsequently metabolized to its hormonally active ... ...

Abstract	Vitamin D has a key role in stimulating calcium absorption from the gut and promoting skeletal health, as well as many other important physiological functions. Vitamin D is produced in the skin. It is subsequently metabolized to its hormonally active form, 1,25-dihydroxyvitamin D (1,25(OH)
MeSH term(s)	Animals ; Humans ; Receptors, Calcitriol/genetics ; Transcription, Genetic/genetics ; Vitamin D/analogs & derivatives ; Vitamin D/metabolism
Chemical Substances	Receptors, Calcitriol ; Vitamin D (1406-16-2) ; 1,25-dihydroxyvitamin D (66772-14-3)
Language	English
Publishing date	2020-02-06
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2489381-X
ISSN	1759-5037 ; 1759-5029
ISSN (online)	1759-5037
ISSN	1759-5029
DOI	10.1038/s41574-019-0312-5
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Article ; Online: Vitamin D deficiency: protective against enteric infection?

Christakos, Sylvia

American journal of physiology. Gastrointestinal and liver physiology

2012 Volume 303, Issue 12, Page(s) G1297–8

MeSH term(s)	Animals ; Calcitriol/adverse effects ; Citrobacter rodentium/immunology ; Enterobacteriaceae Infections/chemically induced ; Enterobacteriaceae Infections/immunology ; Immunocompromised Host/immunology ; Intestinal Mucosa/immunology ; Male ; Th17 Cells/immunology
Chemical Substances	Calcitriol (FXC9231JVH)
Language	English
Publishing date	2012-11-01
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	603840-2
ISSN	1522-1547 ; 0193-1857
ISSN (online)	1522-1547
ISSN	0193-1857
DOI	10.1152/ajpgi.00405.2012
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Article ; Online: Recent advances in our understanding of 1,25-dihydroxyvitamin D(3) regulation of intestinal calcium absorption.

Christakos, Sylvia

Archives of biochemistry and biophysics

2012 Volume 523, Issue 1, Page(s) 73–76

Abstract: Calcium is required for many cellular processes including muscle contraction, nerve pulse transmission, stimulus secretion coupling and bone formation. The principal source of new calcium to meet these essential functions is from the diet. Intestinal ... ...

Abstract	Calcium is required for many cellular processes including muscle contraction, nerve pulse transmission, stimulus secretion coupling and bone formation. The principal source of new calcium to meet these essential functions is from the diet. Intestinal absorption of calcium occurs by an active transcellular path and by a non-saturable paracellular path. The major factor influencing intestinal calcium absorption is vitamin D and more specifically the hormonally active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). This article emphasizes studies that have provided new insight related to the mechanisms involved in the intestinal actions of 1,25(OH)(2)D(3). The following are discussed: recent studies, including those using knock out mice, that suggest that 1,25(OH)(2)D(3) mediated calcium absorption is more complex than the traditional transcellular model; evidence for 1,25(OH)(2)D(3) mediated active transport of calcium by distal as well as proximal segments of the intestine; 1,25(OH)(2)D(3) regulation of paracellular calcium transport and the role of 1,25(OH)(2)D(3) in protection against mucosal injury.
MeSH term(s)	Aging/metabolism ; Animals ; Calcitriol/metabolism ; Calcium/metabolism ; Humans ; Intestinal Absorption ; Intestinal Mucosa/injuries ; Intestinal Mucosa/metabolism ; Phosphates/metabolism
Chemical Substances	Phosphates ; Calcitriol (FXC9231JVH) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2012-01-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	523-x
ISSN	1096-0384 ; 0003-9861
ISSN (online)	1096-0384
ISSN	0003-9861
DOI	10.1016/j.abb.2011.12.020
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Article ; Online: Regulatory domains controlling high intestinal vitamin D receptor gene expression are conserved in mouse and human.

Fleet, James C / Aldea, Dennis / Chen, Lei / Christakos, Sylvia / Verzi, Michael

The Journal of biological chemistry

2022 Volume 298, Issue 3, Page(s) 101616

Abstract: Vitamin D receptor (VDR) levels are highest in the intestine where it mediates 1,25 dihydroxyvitamin D-induced gene expression. However, the mechanisms controlling high intestinal VDR gene expression are unknown. Here, we used Assay for Transposase- ... ...

Abstract	Vitamin D receptor (VDR) levels are highest in the intestine where it mediates 1,25 dihydroxyvitamin D-induced gene expression. However, the mechanisms controlling high intestinal VDR gene expression are unknown. Here, we used Assay for Transposase-Accessible Chromatin using Sequencing (ATAC-Seq) to identify the regulatory sites controlling intestine-specific Vdr gene expression in the small intestine (villi and crypts) and colon of developing, adult, and aged mice. We identified 17 ATAC peaks in a 125 kb region from intron 3 to -55.8 kb from exon 1 of the Vdr gene. Interestingly, many of these peaks were missing/reduced in the developing intestine. Chromatin ImmunoPrecipitation-Sequencing (ChIP-Seq) peaks for intestinal transcription factors (TFs) were present within the ATAC peaks and at HiChIP looping attachments that connected the ATAC/TF ChIP peaks to the transcription start site and CCCTF-binding factor sites at the borders of the Vdr gene regulatory domain. Intestine-specific regulatory sites were identified by comparing ATAC peaks to DNAse-Seq data from other tissues that revealed tissue-specific, evolutionary conserved, and species-specific peaks. Bioinformatics analysis of human DNAse-Seq peaks revealed polymorphisms that disrupt TF-binding sites. Our analysis shows that mouse intestinal Vdr gene regulation requires a complex interaction of multiple distal regulatory regions and is controlled by a combination of intestinal TFs. These intestinal regulatory sites are well conserved in humans suggesting that they may be key components of VDR regulation in both mouse and human intestines.
MeSH term(s)	Animals ; Deoxyribonucleases/genetics ; Gene Expression ; Gene Expression Regulation ; Humans ; Intestines/metabolism ; Mice ; Receptors, Calcitriol/biosynthesis ; Receptors, Calcitriol/genetics ; Receptors, Calcitriol/metabolism ; Transcription Factors/metabolism
Chemical Substances	Receptors, Calcitriol ; Transcription Factors ; VDR protein, human ; Vdr protein, mouse ; Deoxyribonucleases (EC 3.1.-)
Language	English
Publishing date	2022-01-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2022.101616
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Article ; Online: Biology and Mechanisms of Action of the Vitamin D Hormone.

Pike, J Wesley / Christakos, Sylvia

Endocrinology and metabolism clinics of North America

2017 Volume 46, Issue 4, Page(s) 815–843

Abstract: The central role of hormonal 1,25-dihydroxyvitamin ... ...

Abstract	The central role of hormonal 1,25-dihydroxyvitamin D
MeSH term(s)	Animals ; Bone and Bones/metabolism ; Calcitriol/metabolism ; Calcium/metabolism ; Homeostasis/physiology ; Humans ; Receptors, Calcitriol/physiology ; Signal Transduction/physiology ; Vitamin D/physiology
Chemical Substances	Receptors, Calcitriol ; Vitamin D (1406-16-2) ; Calcitriol (FXC9231JVH) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	92116-6
ISSN	1558-4410 ; 0889-8529
ISSN (online)	1558-4410
ISSN	0889-8529
DOI	10.1016/j.ecl.2017.07.001
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