title: Receptor activator of NF-kappaB (RANK) stimulates the proliferation of epithelial cells of the epidermo-pilosebaceous unit.
abstract: Receptor activator of NF-κB (RANK), known for controlling bone mass, has been recognized for its role in epithelial cell activation of the mammary gland. Because bone and the epidermo-pilosebaceous unit of the skin share a lifelong renewal activity where similar molecular players operate, and because mammary glands and hair follicles are both skin appendages, we have addressed the function of RANK in the hair follicle and the epidermis. Here, we show that mice deficient in RANK ligand (RANKL) are unable to initiate a new growth phase of the hair cycle and display arrested epidermal homeostasis. However, transgenic mice overexpressing RANK in the hair follicle or administration of recombinant RANKL both activate the hair cycle and epidermal growth. RANK is expressed by the hair follicle germ and bulge stem cells and the epidermal basal cells, cell types implicated in the renewal of the epidermo-pilosebaceous unit. RANK signaling is dispensable for the formation of the stem cell compartment and the inductive hair follicle mesenchyme, and the hair cycle can be rescued by Rankl knockout skin transplantation onto nude mice. RANKL is actively transcribed by the hair follicle at initiation of its growth phase, providing a mechanism for stem cell RANK engagement and hair-cycle entry. Thus, RANK-RANKL regulates hair renewal and epidermal homeostasis and provides a link between these two activities.
authors.affiliation: Centre National de la Recherche Scientifique, Laboratory of Therapeutic Immunology and Chemistry, Unité Propre de Recherche 9021, Institut de Biologie Moléculaire et Cellulaire, University of Strasbourg, 67084 Strasbourg, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Duheron
authors.forename: Estelle
authors.initials: E
authors.lastname: Hess
authors.forename: Monique
authors.initials: M
authors.lastname: Duval
authors.forename: Marion
authors.initials: M
authors.lastname: Decossas
authors.forename: Beatriz
authors.initials: B
authors.lastname: Castaneda
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Klöpper
authors.forename: Leonela
authors.initials: L
authors.lastname: Amoasii
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Barbaroux
authors.forename: Ifor R
authors.initials: IR
authors.lastname: Williams
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Josef
authors.initials: J
authors.lastname: Penninger
authors.forename: Yongwon
authors.initials: Y
authors.lastname: Choi
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lézot
authors.forename: Richard
authors.initials: R
authors.lastname: Groves
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Mueller
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D018859:Hair Follicle / Q000166:cytology* / Q000502:physiology; D006706:Homeostasis; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics / Q000378:metabolism*; D016038:Skin Transplantation; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
chemical_list: D016328:NF-kappa B; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B