Open Access1α,25‐Dihydroxyvitamin D 3 Modulates the Hair‐Inductive Capacity of Dermal Papilla Cells: Therapeutic Potential for Hair Regeneration
Author(s) -
Aoi Noriyuki,
Inoue Keita,
Chikanishi Toshihiro,
Fujiki Ryoji,
Yamamoto Hanako,
Kato Harunosuke,
Eto Hitomi,
Doi Kentaro,
Itami Satoshi,
Kato Shigeaki,
Yoshimura Kotaro
Publication year - 2012
Publication title -
stem cells translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.781
H-Index - 71
eISSN - 2157-6580
pISSN - 2157-6564
DOI - 10.5966/sctm.2012-0032
Subject(s) - downregulation and upregulation , retinoic acid , calcitriol receptor , wnt signaling pathway , microbiology and biotechnology , hair follicle , biology , cancer research , dermal papillae , regeneration (biology) , endocrinology , signal transduction , vitamin d and neurology , cell culture , biochemistry , gene , genetics
Dermal papilla cells (DPCs) have the potential to induce differentiation of epithelial stem cells into hair, and Wnt signaling is deeply involved in the initiation process. The functional limitation of expanded adult DPCs has been a difficult challenge for cell‐based hair regrowth therapy. We previously reported that 1α,25‐dihydroxyvitamin D 3 (VD 3 ) upregulates expression of transforming growth factor (TGF)‐β2 and alkaline phosphatase (ALP) activity, both features of hair‐inducing human DPCs (hDPCs). In this study, we further examined the effects and signaling pathways associated with VD 3 actions on DPCs. VD 3 suppressed hDPC proliferation in a dose‐dependent, noncytotoxic manner. Among the Wnt‐related genes investigated, Wnt10b expression was significantly upregulated by VD 3 in hDPCs. Wnt10b upregulation, as well as upregulation of ALPL (ALP, liver/bone/kidney) and TGF‐β2, by VD 3 was specific in hDPCs and not detected in human dermal fibroblasts. Screening of paracrine or endocrine factors in the skin indicated that all‐trans retinoic acid (atRA) upregulated Wnt10b gene expression, although synergistic upregulation (combined atRA and VD 3 ) was not seen. RNA interference with vitamin D receptor (VDR) revealed that VD 3 upregulation of Wnt10b, ALPL, and TGF‐β2 was mediated through the genomic VDR pathway. In a rat model of de novo hair regeneration by murine DPC transplantation, pretreatment with VD 3 significantly enhanced hair folliculogenesis. Specifically, a greater number of outgrowing hair shafts and higher maturation of regenerated follicles were observed. Together, these data suggest that VD 3 may promote functional differentiation of DPCs and be useful in preserving the hair follicle‐inductive capacity of cultured DPCs for hair regeneration therapies.