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 ß-catenin accumulation, indicative of Wnt/β-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/ß-catenin pathway.

A comprehensive understanding of androgen-deregulated DPC factors and their effects on differentiating HFSC would help to improve treatments for AGA.

毛囊周期性再生受上皮-间充质相互作用的调节。在雄激素性脱发 (AGA) 期间，毛囊干细胞 (HFSC) 分化因真皮乳头细胞 (DPC) 分泌因子的失调而受损。我们分析了雄激素对 DPC 中 BMPs 表达的影响及其对 HFSC 向头发谱系分化的影响。

雄激素下调 DPC 球体中的 BMP2 和 BMP4。BMP2 的添加恢复了碱性磷酸酶活性，DPC 中毛发诱导的标志物，以及 DPC 诱导的 HFSC 分化，两者都被雄激素抑制。同时，在区分 HFSC 时，检测到 BMPRIa 和 BMPRII 受体的上调以及核 ß-catenin 积累，表明 Wnt/β-catenin 通路激活。

我们的结果表明 BMP2 作为雄激素下调的旁分泌因子，有助于 DPC 诱导并有利于 DPC 诱导的 HFSC 分化为头发谱系，可能是通过与 Wnt/ß-catenin 通路的串扰。

全面了解雄激素失调的 DPC 因素及其对区分 HFSC 的影响将有助于改善 AGA 的治疗。