Vitamin D Receptor Is Essential For Normal Keratinocyte Stem Cell Function

May 2007 in “ Proceedings of the National Academy of Sciences ”

Luisella Cianferotti, Megan Cox, Kristi Skorija, Marie B. Demay

vitamin D receptor VDR keratinocyte stem cell hair follicle cycling alopecia Wnt signaling β-catenin Lef1 sebaceous gland lipid-laden dermal cysts

Studysummary 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.

Our plain-language summary. Not medical advice or a treatment recommendation. Consult a qualified healthcare professional before changing treatment. Full disclaimer

The study found that the vitamin D receptor (VDR) was essential for normal keratinocyte stem cell function and hair follicle cycling, which was crucial for preventing alopecia. In VDR-null mice, hair follicle development was normal, but postmorphogenic hair cycling was impaired due to defects in keratinocyte stem cell self-renewal or lineage specification. This impairment led to alopecia, increased sebaceous gland activity, and lipid-laden dermal cysts, similar to impaired Wnt signaling. The study showed that VDR was necessary for proper Wnt signaling, as it formed a complex with β-catenin and Lef1, crucial for gene activation in keratinocytes. Keratinocyte-specific expression of a VDR transgene corrected these defects, underscoring VDR's role in maintaining hair follicle homeostasis and its potential in preventing hair loss.

View this study on pnas.org →

Discuss this study in the Community →

Research cited in this study

18 / 18 results

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 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 Hair Follicle Stem Cells: Insights from the 2003 Workshop

142 citations , June 2003 in “The journal of investigative dermatology. Symposium proceedings/The Journal of investigative dermatology symposium proceedings”

This workshop overview concluded that follicular epithelial stem cells are multipotent and located in the bulge region of hair follicles, contributing to hair, epidermis, and sebaceous gland formation.

research Enrichment for Living Murine Keratinocytes from the Hair Follicle Bulge with the Cell Surface Marker CD34

561 citations , April 2003 in “Journal of Investigative Dermatology”

CD34 is a marker for isolating stem-like cells in mouse hair follicles.

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.

Targeted Expression of Human Vitamin D Receptor in the Skin Promotes the Initiation of the Postnatal Hair Follicle Cycle and Rescues Alopecia in Vitamin D Receptor Null Mice

research Targeted Expression of Human Vitamin D Receptor in the Skin Promotes the Initiation of the Postnatal Hair Follicle Cycle and Rescues Alopecia in Vitamin D Receptor Null Mice

57 citations , April 2002 in “The journal of investigative dermatology/Journal of investigative dermatology”

This study found that the vitamin D receptor is crucial for initiating the postnatal hair follicular cycle in mice, preventing alopecia associated with its inactivation.

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 Tcf3 and Lef1 Regulate Lineage Differentiation of Multipotent Stem Cells in Skin

555 citations , July 2001 in “Genes & Development”

This study found that Tcf3 and Lef1 differently regulate cell differentiation in multipotent skin stem cells, with Tcf3 promoting follicle-like features and Lef1, when modified, promoting sebocyte differentiation.

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 Involvement of Follicular Stem Cells in Forming Not Only the Follicle but Also the Epidermis

1010 citations , August 2000 in “Cell”

In this study, researchers found that hair follicle stem cells in mice can generate both hair follicle and epidermis cells, highlighting their potential bipotency.

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 Multiple Roles for Activated LEF/TCF Transcription Complexes During Hair Follicle Development and Differentiation

990 citations , October 1999 in “Development”

This study found that LEF1/TCF3 is necessary but not sufficient for TOPGAL activation in hair follicle development, indicating complex regulation in the skin.

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 Alopecia Universalis Associated With a Mutation in the Human Hairless Gene

412 citations , January 1998 in “Science”

This study identified a missense mutation in the human hairless gene associated with a rare form of recessively inherited alopecia universalis, pinpointed on chromosome 8p12.