Cross-talk between bone morphogenetic proteins (BMPs) and WNT signaling pathways in hair follicle stem cells differentiation. Implication in androgenetic alopecia.

CERUTI, JULIETA MARÍA; OPPENHEIMER, FLORENCIA MAIA; LEIRÓS, GUSTAVO JOSÉ; BALAÑÁ, MARÍA EUGENIA

Mar de Plata

Congreso; LXIII Reunion Anual de la Sociedad Argentina de Investigación Clínica; 2018

SAIC

Hair follicle (HF) cyclical growth is governed by interactions between dermal papilla cells (DPC) and epidermal HF stem cells (HFSC). During androgenetic alopecia (AGA) androgens deregulate these interactions and impair HFSC differentiation through inhibition of the Wnt/ B catenin signaling pathway. BMPs and WNTs act on DPC to maintain hair-inducing activity. We studied the role of BMPs on DPC spheres (DPC Sph)- induced HFSC differentiation. The activity of alkaline phosphatase, marker of hair inductivity, decreased in DPC Sph treated with DHT and the addition of BMP2 restored it. Conditioned media from DPC Sph induced HFSC hair-linage differentiation. When these media were conditioned in presence of DHT, HFSC-differentiation was impaired, however, when DPC Sph media were conditioned in presence of DHT and BMP-2, HFSC-differentiation was recovered, suggesting that BMPs can overcome the inhibitory effect of DHT on HFSC differentiation.To deepen in the mechanism by which BMPs could be exerting this pro- differentiating activity, we analyzed the beta-catenin nuclear translocation in HFSC. When BMP2 was added to the DPC Sph conditioned media, beta-catenin translocation was favored in differentiating HFSC compared with conditioned media alone or with DHT, implicating a cross-talk between BMPs and WNT signaling pathway in HFSC. We then analyzed, two WNT pathway inhibitors. CXXC5 mRNA was downregulated in differentiated HFSC independently of the presence of DHT or BMP2 in conditioned media. GSK-3 phosphorylation was not modified by BMP2, as it was in presence of LiCl, a known inhibitor of GSK-3. Even if further studies are necessary to elucidate at which level the cross-interactions of BMP and Wnt signaling may occur, BMPs contribute to DPC inductivity and HFSC differentiation. We conclude that BMPs are critical factors of the complex epithelial-mesenchymal interaction and their downregulation contribute to AGA development.