Vitamin D Receptor Is Essential For Normal Keratinocyte Stem Cell Function

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.