Growth and differentiation of postnatal hair follicles (HF) are controlled by dermal papilla cells (DPC) and HF epidermal stem cells (HFSC) interactions. Even if the molecular nature of these interactions is unclear, signalling molecules as WNTs and BMPs have been involved. During androgenetic alopecia (AGA) androgens cause HF miniaturization and baldness. We reported that androgens abrogate DPC-induced HFSC differentiation suggesting that DPC-secreted factors involved in normal HFSC differentiation are deregulated. Bone morphogenetic proteins (BMPs) act on DPC to maintain key signature features and hair-inducing activity. DPC cultured as monolayer (ML) loss their hair inductive capacity with passages, however, the culture of DPC as spheroids (DPC- Sph), contributes in restoring their inductive properties. We analyzed BMP-2 and BMP-4 mRNA expression in androgen responsive DPC cultured as ML or as DPC-Sph. In DPC-Sph, dihydrotestosterone (DHT) significantly downregulated the expression of both BMPs mRNA. However, only BMP-2 was downregulated in ML. When comparing their basal expression level, a significant higher amount of both BMPs was detected in DPC-Sph. The activity of alkaline phosphatase, used as an indicator for hair inductivity, decreased in DPC-Sph treated with DHT and the addition of recombinant BMP-2 restored it. Conditioned media from DPC-Sph induce HFSC hair-linage differentiation. When these media were conditioned in presence of DHT, HFSC-differentiation was impaired. In order to evaluate the role of BMPs in DPC-induced HFSC differentiation, BMP-2 or BMP-4 were added to conditioned media from DPC-Sph cultured in presence of DHT. These media recovered the ability to differentiate HFSC, suggesting that BMPs can overcome the effect of DHT on the inhibition of HFSC differentiation. We conclude that BMPs are critical factors of the complex epithelial–mesenchymal interactions which contribute to DPC inductivity and HFSC differentiation. Therefore, BMPs dowregulation by androgen would contribute to AGA development.

BONE MORPHOGENETIC PROTEINS ARE CRITICAL FACTORS FOR HAIR FOLLICLE EPITHELIAL –MESENCHYMAL INTERACTIONS IN ANDROGENETIC ALOPECIA