2.      T-flavanone suppresses BMP-4 production in dermal papilla cells.
Shigeru Moriwaki, Azumi Nagasawa, Michiyo Sasajima, Noriko Itou, Akira Hachiya, Takashi Kitahara,  Kao Corporation Biological Science Laboratories, Japan

The results from our recent study suggest that there are multiple pathways through which t-flavanone stimulates hair growth. One such pathway previously reported was t-flavanone's suppression of TGF-b2 activation on keratinocytes (10th EHRS, Barcelona, 2003). In this study, we identified another pathway by focusing on dermal papilla cells, which secrete many hair growth-related molecules. We found that conditioned medium collected from dermal papilla cells that had been treated with t-flavanone induced keratinocyte proliferation.
Gene Chip and RT-PCR analysis revealed that t-flavanone decreased the mRNA expression of BMP-4 in a dose-dependent manner. The expression and secretion of BMP-4 protein also decreased in a similar manner. Furthermore, the addition of recombinant BMP-4 to keratinocytes suppressed their proliferation. In contrast, the addition of a BMP-4 neutralizing antibody into an untreated dermal papilla cell-derived conditioned medium promoted keratinocyte proliferation in a dose-dependent manner. These results indicate that t-flavanone stimulates hair growth by suppressing BMP-4 in dermal papilla cells as well as by suppressing activation of TGF-b2 on keratinocytes.