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Cited by 761Vitamin D Research StudiesParathyroid Disorders and TreatmentsVitamin K Research Studies

The DOI matches its Crossref record; 134 of the 134 references it cites were found in a registry or an index.

Molecular Mechanisms of Vitamin D Action

Haussler, Mark R., Whitfield, G. Kerr, Kaneko, Ichiro, Haussler, Carol A., Hsieh, David, Hsieh, Jui-Cheng, Jurutka, Peter W.·2013·Calcified Tissue International
DOI 10.1007/s00223-012-9619-0
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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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  1. Yamamoto Y, Memezawa A, Takagi K, Ochiai E, Shindo M, Kato S (2009) A tissue-specific function by unliganded VDR. In: Abstracts from the 14th Workshop on Vitamin D, Brugge, Belgium, October 4–8, 2009, p 66

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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.
ORCID
Venue
Calcified Tissue International
Publisher
Springer Science and Business Media LLC
Published
2012-07-11
Volume
92
Issue
2
Pages
77-98
ISSN
  • 0171-967X (ISSN-L)
  • 1432-0827
DOI
10.1007/s00223-012-9619-0
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

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