The Vitamin D Receptor, the Skin and Stem Cells.

J Steroid Biochem Mol Biol. 2010 Feb 4.
The Vitamin D Receptor, the Skin and Stem Cells.

Luderer HF, Demay MB.

Endocrine Unit Massachusetts General Hospital and Harvard Medical School, 50 Blossom St, Thier 11, Boston MA USA 02114.

The active metabolite of vitamin D, 1,25-dihydroxyvitamin D, has been shown to have pro-differentiation and anti-proliferative effects on keratinocytes, that are mediated by interactions with its nuclear receptor. Other cutaneous actions of the Vitamin D receptor have been brought to light by the cutaneous phenotype of humans and mice with non-functional vitamin D receptors. Although mice lacking functional vitamin D receptors develop a normal first coat of hair, they exhibit impaired cyclic regeneration of hair follicles that leads to the development of alopecia. Normal hair cycling involves reciprocal interactions between the dermal papilla and the epidermal keratinocyte. Studies in mice with targeted ablation of the Vitamin D receptor demonstrate that the abnormality in the hair cycle is due to a defect in the keratinocyte component of the hair follicle. Furthermore, expression of mutant Vitamin D receptor transgenes in the keratinocytes of Vitamin D receptor knockout mice demonstrates that the effects of the receptor that maintain hair follicle homeostasis are ligand-independent. Absence of a functional Vitamin D receptor leads to impaired function of keratinocyte stem cells, both in vivo and in vitro. This is manifested by impaired cyclic regeneration of the hair follicle, a decrease in bulge keratinocyte stem cells with ageing and an abnormality in lineage progression of these cells, leading to their preferential differentiation into sebocytes. Copyright 2010. Published by Elsevier Ltd.