Cross-interactions of BMP and WNT signaling pathways attenuate androgen effect on HFSC differentiation

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

JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2019 vol. 139

1087-0024

Hair follicle (HF) cyclical growth is ruled by interactions between dermal papilla cells (DPC)and epidermal HF stem cells (HFSC). In androgenetic alopecia (AGA) androgens deregulate these interactionsimpairing HFSC differentiation. BMPs and WNTs maintain hair-inducing activity of DPC. We studied the role ofBMPs on HFSC differentiation process to follicular linage, induced by DPC, and on its inhibition by androgens.The activity of alkaline phosphatase, marker hair inductivity, decreased in DPC spheres treated with DHT, andit was restored by the addition of BMP2. HFSC hair-linage differentiation was induced by conditioned mediafrom DPC spheres. Media conditioned in presence of DHT, impaired HFSC differentiation, however, when DPCspheres media were conditioned in presence of DHT and BMP-2, or BMP2 was added to media before use,HFSC differentiation was recovered, suggesting that BMPs can overcome the inhibitory effect of DHT onHFSC differentiation. This effect of BMP2 was reproduced in heterotypic spheres composed of DPC andHFSC. It is known that Wnt/ ß-catenin signaling activation is necessary for HFSC differentiation. To deepen inthe mechanism by which BMPs could be exerting the pro- differentiating activity, we analyzed the ß-cateninnuclear translocation in HFSC. When BMP2 was added to DPC spheres conditioned media, ß-catenintranslocation 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. Moreover, we found lowerexpression of Dkk-1, a known WNT signaling inhibitor, in BMP-2 treated DPC spheres. Even if further studiesare necessary to elucidate at which level the cross-interactions of BMP and WNT signaling may occur, BMPscontribute to DPC inductivity and HFSC differentiation. We conclude that BMPs are critical factors of thecomplex epithelial-mesenchymal interaction and their downregulation contribute to AGA development.