580 Hair growth stimulation effects of b-catenin stimulating peptides through DKK-1 inhibition

Alopecia is a common skin disorder known to be induced by both extrinsic factors including oxidative stress, exposure to excessive heat and pollution, and intrinsic factors such as inflammation and genetic disposition. Through the hair growth cycles, hair grows in anagen phase and stops growth in catagen phase, then enters telogen phase of resting stage. Based on hair growth cycle, increasing the hair follicles in the anagen stage and decreasing the follicles in catagen and telogen stage is commonly adopted strategy for treating hair loss or alopecia. Wnt/β-catenin signaling pathway is known to be importantly involved in hair follicle morphogenesis, and stimulation of β-catenin signaling is known to induce an anagen phase. Wnt/β-catenin inhibitor Dickkopf (DKK)-1 binds to low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6), and binding of DKK1 results in phosphorylation of β-catenin and inactivation. In order to develop new anti-hair loss ingredients, new peptide molecules based of LRP5/6 sequence were synthesized and their activity was explored. Using cultured human dermal papillar (hDP) cells, changes of β-catenin signaling molecules and expressions of hair cycle-related growth factors was were measured. As results, several new peptides were identified as having a significant stimulating activity on β-catenin signaling and growth factor expressions as well, at least in part, through the DKK-1 mediated signaling pathway. In hair follicle organ culture model, selected peptide showed a hair shaft elongation activity. In conclusion, these results suggest that Wnt/β-catenin/DKK-1 signaling is important for hair cycle modulation and DKK-1 inhibiting peptide can be used for hair growth through β-catenin signaling stimulation.