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

JULIETA MARÍA CERUTI; GUSTAVO JOSÉ LEIRÓS; ANA GABRIELA KUSINSKY; MARIA EUGENIA BALAÑA

Rotterdam

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

European Society for Dermatological Research (ESDR).

Androgenetic alopecia (AGA) is the most common type of alopecia in men. Androgens action causesHF miniaturization and baldness through mechanisms which remain unclear. Hair follicle (HF) formation begins whensignals from the mesenchyme-derived dermal papilla cells reach multipotent epidermal stem cells in the bulge region(HFSC). We previously reported that androgens abrogate dermal papilla-induced hair follicle differentiation via theinhibition of the canonical Wnt signalling pathway suggesting that androgens deregulate DPC-secreted factorsinvolved in normal HF 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 in follicularkeratinocytes. The aim of this work was to determine if DKK-1 is involved in the differentiation of HFSC.DKK-1 mRNA expression induced by DHT was compared in androgen responsive dermal papilla cells (DPC) culturedas monolayer or as spheroids cell aggregates. In both culture conditions DHT induced approximately 40 times theexpression of DKK-1 mRNA. Nevertheless its basal expression level was significantly lower in spheroid cultureconditions. hDkk-1 treatment in DPC revealed a decrease in the cytoplasmic ⁄total b-catenin protein ratio indicative ofcanonical Wnt pathway inhibition.We used the media conditioned by DPC to induce HFSC hair-linage differentiation. Conditioned media obtained fromDPC, cultured in presence of DKK1, lost its differentiation ability similar to what it was observed in DHT presence.Same results were obtained when conditioned media obtained from DPC were supplemented with DKK-1.These results suggest that DKK-1 may be one paracrine factor induced by DHT that contribute to abrogate