Adenovirus-mediated Wnt5a expression inhibits the telogen-to-anagen transition of hair follicles in mice.

The canonical Wnt/ß-catenin pathway plays an important role in hair cycle induction. Wnt5a is a non-canonical Wnt family member that generally antagonizes canonical Wnt signaling in other systems. In hair follicles, Wnt5a and canonical Wnt are both expressed in cells in the telogen stage. Wnt5a has been shown to be critical for controlling hair cell fate. However, the role that Wnt5a plays in the transition from the telogen to anagen stage is unknown. In this study, using whole-mount in situ hybridization, we show that Wnt5a is produced by several other cell types, excluding dermal papilla cells, throughout the hair cycle. For example, Wnt5a is expressed in bulge and secondary hair germ cells in the telogen stage. Our studies focused on the depilated 8-week-old mouse as a synchronized model of hair growth. Interestingly, overexpression of adenovirus Wnt5a in the dorsal skin of mice led to the elongation of the telogen stage and inhibition of the initiation of the anagen stage. However, following an extended period of time, four pelage hair types grew from hairless skin that was induced by Wnt5a, and the structure of these new hair shafts was normal. Using microarray analysis and quantitative arrays, we showed that the expression of ß-catenin and some target genes of canonical Wnt signaling decreased after Wnt5a treatment. These data demonstrate that Wnt5a may inhibit the telogen stage to maintain a quiescent state of the hair follicle.

Adenovirus-mediated Wnt10b overexpression induces hair follicle regeneration.

Hair follicles periodically undergo regeneration. The balance between activators and inhibitors may determine the time required for telogen hair follicles to reenter anagen. We previously reported that Wnt10b (wingless-type mouse mammary tumor virus integration site family member 10b) could promote the growth of hair follicles in vitro. To unveil the roles of Wnt10b in hair follicle regeneration, we established an in vivo mouse model using intradermal injection. On the basis of this model, we found that Wnt10b could induce the biological switch of hair follicles from telogen to anagen when overexpressed in the skin. The induced hair follicles expressed structure markers and could cycle normally into catagen. Conversely, anagen onset was abrogated by the knockdown of Wnt10b with small interfering RNA (siRNA). The Wnt10b aberrant expression data suggest that it is one of the activators of hair follicle regeneration. The ß-catenin protein is translocated to the nucleus in Wnt10b-induced hair follicles. The biological effects of Wnt10b were abrogated when ß-catenin expression was downregulated with siRNA. These data revealed that Wnt10b might induce hair follicle regeneration in vivo via the enhanced activation of the canonical Wnt signaling pathway. To our knowledge, our data provide previously unreported insights into the regulation of hair follicle cycling and provide potential therapeutic targets for hair follicle-related diseases.

Committed differentiation of hair follicle bulge cells into sebocytes: an in vitro study.

BACKGROUND: Several studies have shown that hair follicle bugle cells can differentiate into hair follicles and contribute to the formation of the epidermis and sebaceous gland. Although many lines of evidence have suggested that the renewal and maintenance of the sebaceous gland depends on hair follicle bulge cells, direct evidence supporting the in vitro differentiation of follicle bulge cells into sebaceous gland cells has not been found. METHODS: Rat vibrissa follicle bulge cells were isolated, cultured, and transfected with green fluorescent protein (GFPC1) plasmids carrying the peroxisome proliferator-activated receptor gamma2 (PPARgamma2 ) gene. The transfected cells were cultured in modified medium, and the morphologic changes of the cells were observed. Moreover, the expression of epithelial membrane antigens (EMAs) by the cells was detected by immunocytochemistry, and adipogenesis of the cells was evaluated. RESULTS: After induction culture, the cell body enlarged gradually and contained abundant cytoplasm; lipid droplets appeared in the cytoplasm of some cells, and the cells resembled sebocytes of the sebaceous gland. The cells were positive on oil red O and EMA staining. The expression of PPARgamma2 mRNA and protein was significantly upregulated in PPARgamma2-transfected cells. The rate of oil red O-stained and EMA-positive cells was higher in PPARgamma2-transfected cells after induction than in bulge-PPARgamma2 cells and non-transfected bulge cells. CONCLUSIONS: Rat vibrissa hair follicle bulge cells may differentiate into sebocytes in vitro, and the PPARgamma2 gene plays a crucial role.