Wnt/β-catenin signaling promotes aging-associated hair graying in mice

// Zhihui Zhang 2,1 , Mingxing Lei 3,4,5 , Haoran Xin 1,6 , Chunyan Hu 1,2 , Tian Yang 1 , Yizhan Xing 1 , Yuhong Li 1 , Haiying Guo 1 , Xiaohua Lian 1 and Fang Deng 1 1 Department of Cell Biology, Third Military Medical University, Chongqing, China 2 Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China 3 Integrative Stem Cell Center, China Medical University Hospital, China Medical University, Taichung, Taiwan 4 “111” Project Laboratory of Biomechanics and Tissue Repair & Key Laboratory of Biorheological Science and Technology of Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China 5 Institute of New Drug Development, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan 6 Student Brigade Camp 3, Third Military Medical University, Chongqing, China Correspondence to: Fang Deng, email: // Keywords : Wnt/β-catenin, hair follicle, aging, melanocytes, hair graying, Gerotarget Received : July 04, 2017 Accepted : August 09, 2017 Published : September 01, 2017 Abstract Canities is an obvious sign of aging in mouse and human, shown as hair graying. Melanocytes in the hair follicle show cyclic activity with hair cycling, which transitions from anagen, catagen to telogen. How the hairs turn gray during aging is not completely uncovered. Here, by using immunostaining and LacZ staining in Dct-LacZ mice, we show that β-catenin is expressed in melanocytes during hair cycling. RT-PCR, western blot and immunostaining show that β-catenin expression is significantly increased in both anagen and telogen skin of aged mice, when compared to the anagen and telogen skin of young mice, respectively. Overexpression of Wnt10b not only accelerates hair follicle to enter anagen phase, but also promotes melanocytes differentiation in young adult mice (2-month old), with increased β-catenin expression in melanocytes at the secondary hair germ and matrix region of regenerated hair follicles. Overexpression of Wnt10b also promotes melanocyte progenitor cells differentiation in vitro . Our data suggest that increased Wnt signaling promotes excessive differentiation of melanocytes, leading to exhaustion of melanocyte stem cells and eventually canities in aged mice.