title: Androgens modify Wnt agonists/antagonists expression balance in dermal papilla cells preventing hair follicle stem cell differentiation in androgenetic alopecia.
abstract: In androgenetic alopecia, androgens impair dermal papilla-induced hair follicle stem cell (HFSC) differentiation inhibiting Wnt signaling. Wnt agonists/antagonists balance was analyzed after dihydrotestosterone (DHT) stimulation in androgen-sensitive dermal papilla cells (DPC) cultured as spheroids or monolayer. In both culture conditions, DHT stimulation downregulated Wnt5a and Wnt10b mRNA while the Wnt antagonist Dkk-1 was upregulated. Notably, tissue architecture of DPC-spheroids lowers Dkk-1 and enhances Wnt agonists' basal expression; probably contributing to DPC inductivity. The role of Wnt agonists/antagonists as mediators of androgen inhibition of DPC-induced HFSC differentiation was evaluated. Inductive DPC-conditioned medium supplemented with DKK-1 impaired HFSC differentiation mimicking androgens' action. This effect was associated with inactivation of Wnt/β-catenin pathway in differentiating HFSC by both DPC-conditioned media. Moreover, addition of WNT10b to DPC-medium conditioned with DHT, overcame androgen inhibition of HFSC differentiation. Our results identify DKK1 and WNT10b as paracrine factors which modulate the HFSC differentiation inhibition involved in androgen-driven balding.
authors: Instituto de Ciencia y Tecnología Dr. César Milstein, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Saladillo 2468, C1440FFX, Ciudad de Buenos Aires, Argentina.
authors: Gustavo José
authors: GJ
authors: Leirós
authors: Instituto de Ciencia y Tecnología Dr. César Milstein, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Saladillo 2468, C1440FFX, Ciudad de Buenos Aires, Argentina.
authors: Julieta María
authors: JM
authors: Ceruti
authors: Instituto de Ciencia y Tecnología Dr. César Milstein, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Saladillo 2468, C1440FFX, Ciudad de Buenos Aires, Argentina.
authors: María Lía
authors: ML
authors: Castellanos
authors: Instituto de Ciencia y Tecnología Dr. César Milstein, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Saladillo 2468, C1440FFX, Ciudad de Buenos Aires, Argentina.
authors: Ana Gabriela
authors: AG
authors: Kusinsky
authors: Instituto de Ciencia y Tecnología Dr. César Milstein, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Saladillo 2468, C1440FFX, Ciudad de Buenos Aires, Argentina. Electronic address: mbalana@fundacioncassara.org.ar.
authors: María Eugenia
authors: ME
authors: Balañá
mesh_terms: D000505:Alopecia / Q000235:genetics / Q000473:pathology*; D000728:Androgens / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D018859:Hair Follicle / Q000473:pathology*; D006801:Humans; D008024:Ligands; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051153:Wnt Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors*; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000728:Androgens; D017077:Culture Media, Conditioned; D008024:Ligands; D012333:RNA, Messenger; D051153:Wnt Proteins; D051176:beta Catenin
keywords: Androgenetic alopecia; Dermal papilla; Epidermal stem cells; Epithelial-mesenchymal interactions; Wnt ligands