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

CERUTI JM; OPPENHEIMER, FLORENCIA MAIA; LEIRÓS, GJ; BALAÑÁ, ME

Bordeaux

Congreso; 49th Annual ESDR Meeting; 2019

ESDR

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 deregulatethese interactions impairing HFSC differentiation. BMPs and WNTs maintain hair-inducingactivity of DPC. We studied the role of BMPs on HFSC differentiation process to follicularlinage, induced by DPC, and on its inhibition by androgens. The activity of alkaline phos-phatase, marker hair inductivity, decreased in DPC spheres treated with DHT, and it wasrestored by the addition of BMP2. HFSC hair-linage differentiation was induced by condi-tioned media from DPC spheres. Media conditioned in presence of DHT, impaired HFSCdifferentiation, however, when DPC spheres media were conditioned in presence of DHTandBMP-2, or BMP2 was added to media before use, HFSC differentiation was recovered, sug-gesting that BMPs can overcome the inhibitory effect of DHT on HFSC differentiation. Thiseffect of BMP2 was reproduced in heterotypic spheres composed of DPC and HFSC. It isknown that Wnt/ ß-catenin signaling activation is necessary for HFSC differentiation. Todeepen in the mechanism by which BMPs could be exerting the pro- differentiating activity,we analyzed the ß-catenin nuclear translocation in HFSC. When BMP2 was added to DPCspheres conditioned media, ß-catenin translocation was favored in differentiating HFSCcompared with conditioned media alone or with DHT, implicating a cross-talk between BMPsand WNT signaling pathway in HFSC. Moreover, we found lower expression of Dkk-1, aknown WNT signaling inhibitor, in BMP-2 treated DPC spheres. Even if further studies arenecessary to elucidate at which level the cross-interactions of BMP and WNT signaling mayoccur, BMPs contribute to DPC inductivity and HFSC differentiation. We conclude that BMPsare critical factors of the complex epithelial-mesenchymal interaction and their down-regulation contribute to AGA development.