PMID- 33259912 OWN - NLM STAT- MEDLINE DCOM- 20210812 LR - 20210812 IS - 1872-8057 (Electronic) IS - 0303-7207 (Linking) VI - 520 DP - 2021 Jan 15 TI - Androgens downregulate BMP2 impairing the inductive role of dermal papilla cells on hair follicle stem cells differentiation. PG - 111096 LID - S0303-7207(20)30398-1 [pii] LID - 10.1016/j.mce.2020.111096 [doi] AB - Hair follicle cyclical regeneration is regulated by epithelial-mesenchymal interactions. During androgenetic alopecia (AGA), hair follicle stem cells (HFSC) differentiation is impaired by deregulation of dermal papilla cells (DPC) secreted factors. We analyzed androgen influence on BMPs expression in DPC and their effect on HFSC differentiation to hair lineage. Androgens downregulated BMP2 and BMP4 in DPC spheroids. Addition of BMP2 restored alkaline phosphatase activity, marker of hair-inductivity in DPC, and DPC-induced HFSC differentiation, both inhibited by androgens. Concomitantly, in differentiating HFSC, an upregulation of BMPRIa and BMPRII receptors and nuclear beta-catenin accumulation, indicative of Wnt/beta-catenin pathway activation, were detected. Our results present BMP2 as an androgen-downregulated paracrine factor that contributes to DPC inductivity and favors DPC-induced HFSC differentiation to hair lineage, possibly through a crosstalk with Wnt/beta-catenin pathway. A comprehensive understanding of androgen-deregulated DPC factors and their effects on differentiating HFSC would help to improve treatments for AGA. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Ceruti, Julieta Maria AU - Ceruti JM AD - Instituto de Ciencia y Tecnologia Dr. Cesar Milstein - (Consejo Nacional de Investigaciones Cientificas y Tecnicas CONICET- Fundacion Pablo Cassara), Saladillo 2468, Ciudad de Buenos Aires, C1440FFX, Argentina. FAU - Oppenheimer, Florencia Maia AU - Oppenheimer FM AD - Instituto de Ciencia y Tecnologia Dr. Cesar Milstein - (Consejo Nacional de Investigaciones Cientificas y Tecnicas CONICET- Fundacion Pablo Cassara), Saladillo 2468, Ciudad de Buenos Aires, C1440FFX, Argentina. FAU - Leiros, Gustavo Jose AU - Leiros GJ AD - Instituto de Ciencia y Tecnologia Dr. Cesar Milstein - (Consejo Nacional de Investigaciones Cientificas y Tecnicas CONICET- Fundacion Pablo Cassara), Saladillo 2468, Ciudad de Buenos Aires, C1440FFX, 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- Fundacion Pablo Cassara), Saladillo 2468, Ciudad de Buenos Aires, C1440FFX, Argentina. Electronic address: mbalana@fundacioncassara.org.ar. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201128 PL - Ireland TA - Mol Cell Endocrinol JT - Molecular and cellular endocrinology JID - 7500844 RN - 0 (Androgens) RN - 0 (Biomarkers) RN - 0 (Bone Morphogenetic Protein 2) RN - 0 (Bone Morphogenetic Protein 4) RN - 0 (Culture Media, Conditioned) RN - 0 (Ligands) RN - 0 (beta Catenin) RN - EC 2.7.11.30 (Bone Morphogenetic Protein Receptors) SB - IM MH - Androgens/*pharmacology MH - Biomarkers/metabolism MH - Bone Morphogenetic Protein 2/*genetics/metabolism MH - Bone Morphogenetic Protein 4/metabolism MH - Bone Morphogenetic Protein Receptors/metabolism MH - *Cell Differentiation/drug effects MH - Cell Line MH - Cell Nucleus/drug effects/metabolism MH - Culture Media, Conditioned/pharmacology MH - Dermis/*cytology MH - Down-Regulation/drug effects/*genetics MH - Hair Follicle/*cytology MH - Humans MH - Ligands MH - Protein Transport/drug effects MH - Spheroids, Cellular/cytology/drug effects MH - Stem Cells/cytology/drug effects MH - Wnt Signaling Pathway/drug effects MH - beta Catenin/metabolism OTO - NOTNLM OT - Androgenetic alopecia OT - BMP OT - Dermal papilla OT - Epithelial-mesenchymal interactions OT - WNT EDAT- 2020/12/02 06:00 MHDA- 2021/08/13 06:00 CRDT- 2020/12/01 20:09 PHST- 2020/09/26 00:00 [received] PHST- 2020/11/24 00:00 [revised] PHST- 2020/11/24 00:00 [accepted] PHST- 2020/12/02 06:00 [pubmed] PHST- 2021/08/13 06:00 [medline] PHST- 2020/12/01 20:09 [entrez] AID - S0303-7207(20)30398-1 [pii] AID - 10.1016/j.mce.2020.111096 [doi] PST - ppublish SO - Mol Cell Endocrinol. 2021 Jan 15;520:111096. doi: 10.1016/j.mce.2020.111096. Epub 2020 Nov 28.