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Molecular Mechanisms of Vitamin D Action
Abstract
The hormonal metabolite of vitamin D, 1α,25-dihydroxyvitamin D(3) (1,25D), initiates biological responses via binding to the vitamin D receptor (VDR). When occupied by 1,25D, VDR interacts with the retinoid X receptor (RXR) to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1,25D. By recruiting complexes of either coactivators or corepressors, ligand-activated VDR-RXR modulates the transcription of genes encoding proteins that promulgate the traditional functions of vitamin D, including signaling intestinal calcium and phosphate absorption to effect skeletal and calcium homeostasis. Thus, vitamin D action in a particular cell depends upon the metabolic production or delivery of sufficient concentrations of the 1,25D ligand, expression of adequate VDR and RXR coreceptor proteins, and cell-specific programming of transcriptional responses to regulate select genes that encode proteins that function in mediating the effects of vitamin D. For example, 1,25D induces RANKL, SPP1 (osteopontin), and BGP (osteocalcin) to govern bone mineral remodeling; TRPV6, CaBP(9k), and claudin 2 to promote intestinal calcium absorption; and TRPV5, klotho, and Npt2c to regulate renal calcium and phosphate reabsorption. VDR appears to function unliganded by 1,25D in keratinocytes to drive mammalian hair cycling via regulation of genes such as CASP14, S100A8, SOSTDC1, and others affecting Wnt signaling. Finally, alternative, low-affinity, non-vitamin D VDR ligands, e.g., lithocholic acid, docosahexaenoic acid, and curcumin, have been reported. Combined alternative VDR ligand(s) and 1,25D/VDR control of gene expression may delay chronic disorders of aging such as osteoporosis, type 2 diabetes, cardiovascular disease, and cancer.
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“In summary, vitamin D is responsible for storage of calcium/phosphorus in bone and amino acids in muscle.”
From Interaction of the endocrine system with inflammation: a function of energy and volume regulation (2014) · cites this paper as [29]
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Metadata
- Authors
- Haussler, M. R., Whitfield, G. K., Kaneko, I., Haussler, C. A., Hsieh, D., Hsieh, J.-C., & Jurutka, P. W.
- Affiliations
- University of Arizona College of Medicine- Phoenix (US)
- University of Arizona (US)
- Corresponding author
- Haussler, Mark R.
- Venue
- Calcified Tissue International
- Published
- 2012-07-11
- Volume
- 92
- Issue
- 2
- Pages
- 77-98
- ISSN
- 0171-967X (ISSN-L)
- 1432-0827
- OpenAlex
- W2017851530
- Cited by
- 759
- References
- 132
- Citations by year
- 2026: 37 · 2025: 41 · 2024: 53 · 2023: 54 · 2022: 52 · 2021: 82 · 2020: 79 · 2019: 48 · 2018: 54 · 2017: 58 · 2016: 49 · 2015: 64 · 2014: 54 · 2013: 29 · 2012: 4
- FWCI
- 6.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Calcified Tissue International (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Vitamin D Research Studies
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin K Research Studies
- Keywords
- vitamin D, 1,25-dihydroxyvitamin D3, vitamin D receptor, retinoid X receptor, heterodimer, transcriptional regulation, calcium homeostasis, phosphate homeostasis, intestinal calcium absorption, bone remodeling, RANKL, osteocalcin, osteopontin, renal calcium reabsorption, hair cycle, keratinocytes, Wnt signaling, lithocholic acid, docosahexaenoic acid, curcumin, osteoporosis, type 2 diabetes, cardiovascular disease, cancer
- MeSH terms
- Animals, Gene Expression Regulation, Humans, Vitamin D, Signal Transduction, Receptors, Calcitriol
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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