The Hair Cycle and Vitamin D Receptor

October 2011 in “ Archives of Biochemistry and Biophysics ”

Marie B. Demay

Vitamin D receptor VDR keratinocyte stem cells hair follicle 1,25-dihydroxyvitamin D hair cycle stem cell self-renewal lineage progression

Studysummary This study found that while calcium can substitute for the Vitamin D receptor in maintaining epidermal keratinocyte differentiation, it cannot compensate for hair follicle dysfunction caused by the absence of the receptor. Our plain-language summary of this paper — not a Tressless recommendation.

The study highlighted the critical role of the Vitamin D receptor (VDR) in maintaining hair follicle function, particularly in keratinocyte stem cells located in the bulge region of the hair follicle. While calcium could compensate for the absence of VDR in epidermal keratinocyte differentiation, it could not prevent the hair follicle defects caused by VDR ablation. These defects were independent of 1,25-dihydroxyvitamin D, indicating that VDR's role in hair follicle cycling did not rely on this form of vitamin D. The absence of a functional VDR led to defects in stem cell self-renewal and lineage progression, resulting in the absence of post-morphogenic hair cycles. The specific molecular partners and target genes of VDR in these stem cells were not identified at the time.

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Research cited in this study

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research Lymphoid Enhancer-Binding Factor-1 Interacts with the DNA-Binding Domain of the Vitamin D Receptor

37 citations , April 2011 in “Journal of Biological Chemistry”

This study discovered a novel interaction between the vitamin D receptor and LEF1, essential for normal Wnt signaling in keratinocytes, which is crucial for regular hair cycling.

research Disruption of the Hedgehog Signaling Pathway Contributes to Hair Follicle Cycling Deficiency in VDR Knockout Mice

53 citations , May 2010 in “Journal of Cellular Physiology”

This study found that mice lacking the Vitamin D receptor showed disrupted hair follicle cycling, which was partially restored with hedgehog signaling pathway activation, suggesting a role for this pathway in follicle regulation independent of vitamin D.

research The Vitamin D Receptor Is a Wnt Effector That Controls Hair Follicle Differentiation and Specifies Tumor Type in Adult Epidermis

127 citations , January 2008 in “PloS one”

This study observed that the vitamin D receptor is crucial for hair follicle formation and altering tumor development in the Wnt signaling pathway, suggesting therapeutic potential for vitamin D analogues in related tumors.

research Vitamin D Receptor Is Essential For Normal Keratinocyte Stem Cell Function

143 citations , May 2007 in “Proceedings of the National Academy of Sciences”

This study found that absence of the vitamin D receptor in keratinocytes impairs canonical Wnt signaling and leads to alopecia due to defects in keratinocyte stem cells.

research Hairless Suppresses Vitamin D Receptor Transactivation in Human Keratinocytes

78 citations , November 2005 in “Endocrinology”

This study found that Hairless (Hr) acts as a corepressor of the vitamin D receptor (VDR) in human keratinocytes, blocking the action of vitamin D on keratinocyte differentiation.

research Hairless Triggers Reactivation of Hair Growth by Promoting Wnt Signaling

137 citations , September 2005 in “Proceedings of the National Academy of Sciences of the United States of America”

In this study, researchers found that transgenic expression of the Hairless gene in keratinocytes can restore hair follicle regeneration in Hr-deficient mice by repressing Wise, a modulator of Wnt signaling.

research Ligand-Independent Actions of the Vitamin D Receptor Maintain Hair Follicle Homeostasis

144 citations , December 2004 in “Molecular Endocrinology”

This study found that the effects of the vitamin D receptor on hair follicle cycling in mice are independent of its ability to bind a hormone, with specific domain mutations influencing hair regrowth outcomes.

research 25 Hydroxyvitamin D 1 Alpha-Hydroxylase Is Required for Optimal Epidermal Differentiation and Permeability Barrier Homeostasis

140 citations , April 2004 in “The journal of investigative dermatology/Journal of investigative dermatology”

This study found that mice lacking the 1αOHase enzyme, which is responsible for producing a key vitamin D metabolite, showed impaired epidermal differentiation and delayed recovery of skin barrier function after disruption.

research Transient Activation of Beta-Catenin Signaling in Adult Mouse Epidermis Induces New Hair Follicles, Continuous Activation Maintains Tumors

335 citations , March 2004 in “Development”

This study found that continuous β-catenin signaling in adult mouse epidermis can reprogram hair follicles to form benign tumors, which regress after the signaling is discontinued.

research Physical And Functional Interaction Between The Vitamin D Receptor And Hairless Corepressor, Two Proteins Required For Hair Cycling

215 citations , September 2003 in “Journal of Biological Chemistry”

This study found that the hairless gene product (Hr) suppresses VDR-mediated gene activation by directly interacting with the vitamin D receptor, potentially affecting hair follicle function.

research Deletion of DNA Binding Domain of the Vitamin D Receptor Abrogates Genomic and Nongenomic Functions of Vitamin D

277 citations , July 2002 in “Molecular Endocrinology”

In this study, homozygous VDR null mutant mice exhibited nonfunctional vitamin D receptors, leading to growth abnormalities and revealing the limited physiological importance of vitamin D pathways outside the classical receptor.

research Expression of ΔNLef1 in Mouse Epidermis Results in Differentiation of Hair Follicles into Squamous Epidermal Cysts and Formation of Skin Tumors

297 citations , January 2002 in “Development”

In this study, repressing β-catenin/Lef1 signalling in mouse epidermis led to progressive hair loss, dermal cysts, and spontaneous skin tumors with sebaceous differentiation, indicating altered keratinocyte differentiation and potential tumourigenic processes.

research Lack of the Vitamin D Receptor Is Associated with Reduced Epidermal Differentiation and Hair Follicle Growth

180 citations , January 2002 in “The journal of investigative dermatology/Journal of investigative dermatology”

This study observed that vitamin D receptor knockout mice exhibit impaired epidermal differentiation and progressive hair loss, suggesting the importance of the vitamin D receptor in normal skin and hair follicle development.

research Targeting Expression of the Human Vitamin D Receptor to the Keratinocytes of Vitamin D Receptor Null Mice Prevents Alopecia

115 citations , December 2001 in “Endocrinology”

This study found that restoring vitamin D receptor expression specifically in the keratinocytes of VDR null mice prevented alopecia and enhanced hair follicle response during anagen initiation.

research The Hairless Gene Mutated in Congenital Hair Loss Disorders Encodes a Novel Nuclear Receptor Corepressor

178 citations , October 2001 in “Genes & Development”

This study found that the mammalian hairless gene encodes a corepressor protein that interacts with thyroid hormone receptors, providing insights into hair loss syndromes in humans and mice.

research Metabolic And Cellular Analysis Of Alopecia In Vitamin D Receptor Knockout Mice

137 citations , April 2001 in “Journal of Clinical Investigation”

This study found that alopecia in VDR-null mice persists despite undetectable vitamin D levels, indicating a defect in epithelial-mesenchymal communication due to the absence of ligand-independent receptor function.

research Skin Abnormalities Generated by Temporally Controlled RXRα Mutations in Mouse Epidermis

303 citations , October 2000 in “Nature”

This study found that RXRα plays a critical role in hair cycling and keratinocyte functions in mice, likely through its interaction with VDR in epidermal cells.

research Evaluation of Keratinocyte Proliferation and Differentiation in Vitamin D Receptor Knockout Mice

114 citations , June 2000 in “Endocrinology”

In this study, the researchers found that alopecia in VDR null mice is likely due to issues with hair cycle initiation rather than defects in keratinocyte proliferation or differentiation.

research Induction of the Hair Growth Phase in Postnatal Mice by Localized Transient Expression of Sonic Hedgehog

231 citations , October 1999 in “Journal of Clinical Investigation”

This study found that administering an adenovirus vector to increase Sonic hedgehog gene expression in mouse skin accelerated the transition of hair follicles into the growth phase, promoting hair growth.

research The Biology of Hair Follicles

1113 citations , August 1999 in “The New England Journal of Medicine”

This article discusses the biologic and psychosocial significance of hair, the current limitations in hair growth drugs, and anticipates future therapies based on advancing hair follicle research.

research Normalization of Mineral Ion Homeostasis by Dietary Means Prevents Hyperparathyroidism, Rickets, and Osteomalacia, But Not Alopecia in Vitamin D Receptor-Ablated Mice

519 citations , October 1998 in “Endocrinology”

The study found that normalizing mineral ion levels in vitamin D receptor-ablated mice prevented hyperparathyroidism and bone disorders but did not address hair loss, indicating the VDR's role in hair growth.