PMID- 27769713 OWN - NLM STAT- MEDLINE DCOM- 20170925 LR - 20240109 IS - 1872-8057 (Electronic) IS - 0303-7207 (Linking) VI - 439 DP - 2017 Jan 5 TI - Androgens modify Wnt agonists/antagonists expression balance in dermal papilla cells preventing hair follicle stem cell differentiation in androgenetic alopecia. PG - 26-34 LID - S0303-7207(16)30429-4 [pii] LID - 10.1016/j.mce.2016.10.018 [doi] AB - 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/beta-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. CI - Copyright A(c) 2016 Elsevier Ireland Ltd. All rights reserved. FAU - Leiros, Gustavo Jose AU - Leiros GJ AD - Instituto de Ciencia y Tecnologia Dr. Cesar Milstein, Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Saladillo 2468, C1440FFX, Ciudad de Buenos Aires, Argentina. FAU - Ceruti, Julieta Maria AU - Ceruti JM AD - Instituto de Ciencia y Tecnologia Dr. Cesar Milstein, Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Saladillo 2468, C1440FFX, Ciudad de Buenos Aires, Argentina. FAU - Castellanos, Maria Lia AU - Castellanos ML AD - Instituto de Ciencia y Tecnologia Dr. Cesar Milstein, Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Saladillo 2468, C1440FFX, Ciudad de Buenos Aires, Argentina. FAU - Kusinsky, Ana Gabriela AU - Kusinsky AG AD - Instituto de Ciencia y Tecnologia Dr. Cesar Milstein, Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Saladillo 2468, C1440FFX, Ciudad de Buenos Aires, Argentina. FAU - Balana, Maria Eugenia AU - Balana ME AD - Instituto de Ciencia y Tecnologia Dr. Cesar Milstein, Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Saladillo 2468, C1440FFX, Ciudad de Buenos Aires, Argentina. Electronic address: mbalana@fundacioncassara.org.ar. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161018 PL - Ireland TA - Mol Cell Endocrinol JT - Molecular and cellular endocrinology JID - 7500844 RN - 0 (Androgens) RN - 0 (Culture Media, Conditioned) RN - 0 (Ligands) RN - 0 (RNA, Messenger) RN - 0 (Wnt Proteins) RN - 0 (beta Catenin) SB - IM MH - Alopecia/genetics/*pathology MH - Androgens/*pharmacology MH - Cell Differentiation/*drug effects MH - Cell Line MH - Culture Media, Conditioned/pharmacology MH - Cytoplasm/drug effects/metabolism MH - Hair Follicle/*pathology MH - Humans MH - Ligands MH - RNA, Messenger/genetics/metabolism MH - Stem Cells/drug effects/metabolism/*pathology MH - Wnt Proteins/*agonists/*antagonists & inhibitors MH - Wnt Signaling Pathway/drug effects MH - beta Catenin/metabolism OTO - NOTNLM OT - Androgenetic alopecia OT - Dermal papilla OT - Epidermal stem cells OT - Epithelial-mesenchymal interactions OT - Wnt ligands EDAT- 2016/10/30 06:00 MHDA- 2017/09/26 06:00 CRDT- 2016/11/05 06:00 PHST- 2016/06/06 00:00 [received] PHST- 2016/09/27 00:00 [revised] PHST- 2016/10/17 00:00 [accepted] PHST- 2016/10/30 06:00 [pubmed] PHST- 2017/09/26 06:00 [medline] PHST- 2016/11/05 06:00 [entrez] AID - S0303-7207(16)30429-4 [pii] AID - 10.1016/j.mce.2016.10.018 [doi] PST - ppublish SO - Mol Cell Endocrinol. 2017 Jan 5;439:26-34. doi: 10.1016/j.mce.2016.10.018. Epub 2016 Oct 18.