ANDROGEN-DRIVEN BONE MORPHOGENETIC PROTEINS (BMPS) DOWNREGULATION IN DERMAL PAPILLA CELLS DISRUPTS HAIR FOLLICLE STEM CELLS DIFFERENTIATION.

CERUTI, JULIETA M; KRUM, VALERIA Y; KUSINSKY, AG; BALAÑÁ, ME

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC) 2015. Mar del Plata. Argentina.; 2016

SAIC

Duringandrogenetic alopecia (AGA) androgens cause hair follicle (HF) miniaturizationand baldness through mechanisms which remain unclear. HF formation begins whensignals from the mesenchyme-derived dermal papilla cells (DPC) reachmultipotent epidermal stem cells in the bulge region (HFSC). The HF bulbmicroenvironment is rich in bone morphogenetic proteins (BMPs) that act on DPCto maintain key signature features in vitro and hair-inducing activity in vivo.DPC cultured as monolayer (ML) loss their hair inductive capacity with passages,however, when DPC are cultured as spheroids (DPC-Sph), show an appropriatecellular phenotype and restore inductive properties. We previously reportedthat androgens abrogate DPC-induced hair follicle differentiation suggestingthat androgens deregulate DPC-secreted factors involved in normal HFSC differentiation.The aim of this work was to evaluate if BMPs are involved in DPC-induced HFSCdifferentiation. BMP-2 and BMP-4 mRNA expression was evaluated in androgenresponsive DPC cultured as ML or as DPC-Sph. In DPC-Sph, dihydrotestosterone (DHT)significantly downregulated the expression of both BMP-2 and BMP-4 mRNA.However, only BMP-2 was downregulated in ML. When comparing their basalexpression level, a significant higher amount of both BMPs was detected in DPC-Sph.We then used conditioned media from DPC-Sph to induce HFSC hair-linagedifferentiation. When these media was conditioned in presence of DHT, HFSC-differentiationwas impaired. When BMP-2 or BMP-4 was added to conditioned media from DPC-Sphcultured in presence of DHT, these media recovered the ability to differentiateHFSC. These results suggest that BMPs can overcome the effect of DHT on theinhibition of HFSC differentiation. We conclude that BMPs are critical factorsof the complex epithelial?mesenchymal cross-talk deregulated by androgensduring AGA and are necessary to induce HFSC differentiation.