Dickkopf 1 from Dermal Papilla Cells may contribute to impair hair follicle stem cell differentiation in androgenetic alopecia

CERUTI JM; GUSTAVO JOSÉ LEIROS; KUSINSKY, AG; MARÍA EUGENIA BALAÑA

Rotterdam

Congreso; 45th Annual Meeting of the European Society for Dermatological Research (ESDR); 2015

ESDR

ABSTRACTDickkopf 1 from Dermal Papilla Cells may contribute to impair hair follicle stem cell differentiation in androgenetic alopeciaJ Ceruti, G Leiros, AG Kusinsky and ME Balañá Androgenetic alopecia (AGA) is the most common type of alopecia in men. Androgens actioncauses HF miniaturization and baldness through mechanisms which remain unclear. Hair follicle(HF) formation begins when signals from the mesenchyme-derived dermal papilla cells reach multipotentepidermal stem cells in the bulge region (HFSC). We previously reported that androgensabrogate dermal papilla-induced hair follicle differentiation via the inhibition of the canonical Wntsignalling pathway suggesting that androgens deregulate DPC-secreted factors involved in normalHF stem cell differentiation. On the other hand, Dickkopf 1 (DKK-1), a Wnt antagonist inducible bydihydrotestosterone (DHT) from balding papillae, promotes hair regression and causes apoptosis infollicular keratinocytes. The aim of this work was to determine if DKK-1 is involved in the differentiationof HFSC. DKK-1 mRNA expression induced by DHT was compared in androgen responsivedermal papilla cells (DPC) cultured as monolayer or as spheroids cell aggregates. In both cultureconditions DHT induced approximately 40 times the expression of DKK-1 mRNA. Nevertheless itsbasal expression level was significantly lower in spheroid culture conditions. hDkk-1 treatment inDPC revealed a decrease in the cytoplasmic total b-catenin protein ratio indicative of canonicalWnt pathway inhibition. We used the media conditioned by DPC to induce HFSC hair-linagedifferentiation. Conditioned media obtained from DPC, cultured in presence of DKK1, lost itsdifferentiation ability similar to what it was observed in DHT presence. Same results were obtainedwhen conditioned media obtained from DPC were supplemented with DKK-1. These results suggestthat DKK-1 may be one paracrine factor induced by DHT that contribute to abrogate hair linagedifferentiation of HFSC differentiation explaining in part the pathological effect of androgen in AGA.