Dickkopf 1 Promotes Regression of Hair Follicles

• Published in: Journal of investigative dermatology Vol. 132; no. 6; pp. 1554 - 1560
• Main Authors: Kwack, Mi H., Kim, Moon K., Kim, Jung C., Sung, Young K.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-06-2012; Nature Publishing Group; Elsevier Limited
• Subjects: Alopecia - pathology; Alopecia - physiopathology; Alopecia - therapy; Animals; Antibodies, Neutralizing - pharmacology; bcl-2-Associated X Protein - genetics; beta Catenin - metabolism; Biological and medical sciences; Cells, Cultured; Dermatology; Female; Hair - drug effects; Hair - growth & development; Hair - transplantation; Hair Follicle - drug effects; Hair Follicle - pathology; Hair Follicle - physiology; Humans; Injections, Intradermal; Intercellular Signaling Peptides and Proteins - immunology; Intercellular Signaling Peptides and Proteins - pharmacology; Intercellular Signaling Peptides and Proteins - physiology; Keratinocytes - cytology; Keratinocytes - physiology; Medical sciences; Mice; Mice, Inbred C57BL; Recombinant Proteins - immunology; Recombinant Proteins - pharmacology; RNA, Messenger - metabolism; Signal Transduction - physiology; Wnt Proteins - metabolism; Dermatology; Hair follicle
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/jid.2012.24

Recently, we suggested that Dickkopf 1 (DKK-1) is a pathogenic mediator involved in male pattern baldness. As premature catagen onset is a key characteristic of male pattern baldness, in this study, we evaluated whether DKK-1 has a role as a catagen inducer in hair cycling. Herein, we report that recombinant human DKK-1 (rhDKK-1) injection into the hypodermis of mice during anagen caused premature onset of catagen, whereas neutralizing DKK-1 antibody delayed anagen-to-catagen transition in mice. Moreover, treatment with rhDKK-1 led to a decrease in final hair follicle length, whereas DKK-1 antibody led to an increase compared with control animals. In addition, DKK-1 and DKK-1 messenger RNA expression is most upregulated in follicular keratinocytes of late anagen in depilation-induced hair cycle progression. Moreover, we observed that rhDKK-1 blocks canonical Wnt-mediated activation of β-catenin signaling and induces the proapoptotic protein Bax, resulting in apoptosis in outer root sheath keratinocytes. Taken together, our data strongly suggest that DKK-1 is involved in anagen-to-catagen transition in the hair cycle by regulating the activity of follicular keratinocytes.