A Meeting of Two Chronobiological Systems: Circadian Proteins Period1 and BMAL1 Modulate the Human Hair Cycle Clock

 2014 Mar;134(3):610-619. doi: 10.1038/jid.2013.366. Epub 2013 Sep 4
Al-Nuaimi Y1, Hardman JA2, Bíró T3, Haslam IS1, Philpott MP4, Tóth BI3, Farjo N5, Farjo B5, Baier G6, Watson REB1, Grimaldi B7, Kloepper JE8, Paus R9
This peer reviewed article of the research below, was published in the September 2013 advanced online edition of the highly influential Journal of Investigative Dermatolgy. The work was a collaboration of :
  • The Dermatology Centre, Salford Royal NHS Foundation Trust;
  • The Institute of Inflammation and Repair, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK;
  • Doctoral Training Centre in Integrative Systems Biology, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK;
  • DE-MTA ‘‘Lendulet’’ Cell Physiology Group, Department of Physiology, University of Debrecen, Debrecen, Hungary;
  • Centre for Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK;
  • Farjo Hair Institute, Manchester, UK;
  • Faculty of Life Sciences, Division of Biosciences, Department of Cell and Developmental Biology, University College London, London, UK;
  • Italian Institute of Technology, Genova, Italy
  • and Department of Dermatology, University of Luebeck, Luebeck, Germany

The hair follicle (HF) is a continuously remodeled mini organ that cycles between growth (anagen), regression (catagen), and relative quiescence (telogen). As the anagen-to-catagen transformation of microdissected human scalp HFs can be observed in organ culture, it permits the study of the unknown controls of autonomous, rhythmic tissue remodeling of the HF, which intersects developmental, chronobiological, and growth-regulatory mechanisms. The hypothesis that the peripheral clock system is involved in hair cycle control, i.e., the anagen-to- catagen transformation, was tested. Here we show that in the absence of central clock influences, isolated, organ- cultured human HFs show circadian changes in the gene and protein expression of core clock genes (CLOCK, BMAL1, and Period1) and clock-controlled genes (c-Myc, NR1D1, and CDKN1A), with Period1 expression being hair cycle dependent. Knockdown of either BMAL1 or Period1 in human anagen HFs significantly prolonged anagen. This provides evidence that peripheral core clock genes modulate human HF cycling and are an integral component of the human hair cycle clock. Specifically, our study identifies BMAL1 and Period1 as potential therapeutic targets for modulating human hair growth.

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