Absence of Vitamin D Receptor-Mediated PPARγ Suppression Causes Alopecia in VDR-Null Mice

December 2016 in “ The FASEB Journal ”

Saini Vaibhav, Zhao Heng-guang, Petit, Elizabeth T., Gori Francesca, Demay Marie B.

vitamin D receptor VDR alopecia keratinocyte stem cell KSC PPARγ PGC1β LPL transcriptional suppressor hair growth hair loss stem cells gene expression

Studysummary This study found that the absence of vitamin D receptor-mediated suppression of PPARγ expression causes hair loss in VDR-null mice.

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

The study investigated the role of the vitamin D receptor (VDR) in hair loss by examining VDR-null (VDR−/−) mice, which exhibited alopecia due to impaired keratinocyte stem cell (KSC) function. RNA sequencing revealed that over 80% of differentially expressed genes were up-regulated in VDR−/− KSCs, indicating that VDR acts as a transcriptional suppressor in wild-type KSCs. Key up-regulated genes included PPARγ, PGC1β, and LPL, which are direct VDR targets. The absence of VDR allowed PPARγ to occupy its regulatory region, unlike in wild-type keratinocytes. Mice with keratinocyte-specific PPARγ haploinsufficiency showed normalized PPARγ mRNA levels and restored hair growth, suggesting that the lack of VDR-mediated PPARγ suppression was responsible for alopecia in VDR−/− mice.

View this study on fasebj.org →

Discuss this study in the Community →

Research cited in this study

22 / 22 results

research Foxc1 Reinforces Quiescence in Self-Renewing Hair Follicle Stem Cells

142 citations , February 2016 in “Science”

This review discusses the role of Foxc1 and type XVII collagen in hair follicle stem cell quiescence and aging, identifying mechanisms that relate to hair thinning and hair loss, and reports no new results.

research The Vitamin D Receptor Is Required for Activation of CWnt and Hedgehog Signaling in Keratinocytes

56 citations , September 2014 in “Molecular Endocrinology”

This study found that the absence of unliganded vitamin D receptor significantly impairs cWnt and hedgehog signaling pathways necessary for hair cycle initiation in VDR-null mice.

research A Humanized Mouse Model of Hereditary 1,25-Dihydroxyvitamin D–Resistant Rickets Without Alopecia

25 citations , August 2014 in “Endocrinology”

This study created a humanized mouse model of hereditary vitamin D-resistant rickets that lacks alopecia, indicating the mutant receptor's potential to explore the syndrome's characteristics beyond vitamin D binding.

research Emerging Interactions Between Skin Stem Cells and Their Niches

426 citations , August 2014 in “Nature Medicine”

This narrative review examines the interactions between skin stem cells and their niches, finding new insights from advancements in genetic and imaging tools but reporting no new experimental results.

research Potential Relationship Between the Canonical Wnt Signaling Pathway and Expression of the Vitamin D Receptor in Alopecia

21 citations , March 2014 in “Clinical and experimental dermatology”

This study observed a potential relationship between the canonical Wnt signalling pathway and the expression of the vitamin D receptor in alopecia, suggesting a link worth further exploration.

research Mutations in the Vitamin D Receptor and Hereditary Vitamin D-Resistant Rickets

107 citations , March 2014 in “BoneKEy Reports”

This abstract reviews hereditary vitamin D-resistant rickets, a rare genetic condition causing severe early childhood rickets, and reports no new results; effective treatment typically requires high doses of calcium to address hypocalcemia and secondary hyperparathyroidism.

research Lipoatrophy and Severe Metabolic Disturbance in Mice with Fat-Specific Deletion of PPARγ

218 citations , October 2013 in “Proceedings of the National Academy of Sciences of the United States of America”

This study found that removing PPARγ specifically from mouse adipose tissue led to severe fat loss, insulin resistance, diabetes, and associated metabolic abnormalities.

research Wnt Signaling in Skin Development, Homeostasis, and Disease

260 citations , December 2012 in “Cold Spring Harbor Perspectives in Biology”

This review discusses the significant role of Wnt signaling in skin development, homeostasis, and disease, highlighting recent advances in understanding its diverse functions, but reports no new experimental results.

research Adipocyte Lineage Cells Contribute to the Skin Stem Cell Niche to Drive Hair Cycling

499 citations , September 2011 in “Cell”

This study found that intradermal adipocyte lineage cells in mice are necessary and sufficient to activate follicular stem cells, highlighting their role in regulating skin stem cell activity.

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 Hair Follicle Expression of 1,25-Dihydroxyvitamin D3 Receptors During the Murine Hair Cycle

95 citations , July 2006 in “British Journal of Dermatology”

This study observed that vitamin D receptor expression in certain hair follicle cells varies throughout the murine hair cycle, suggesting a potential role for 1,25-dihydroxyvitamin D3 in hair follicle biology.

research The Hair Cycle

375 citations , February 2006 in “Journal of Cell Science”

This article reviews the stages and regulation of the hair cycle, highlighting molecular regulators involved, but it does not present new research findings.

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

29 citations , June 2000 in “Endocrinology”

This study suggests that alopecia in vitamin D receptor null mice is due to impaired initiation of the hair cycle rather than defects in keratinocyte proliferation or differentiation.

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.