Receptor activator of NF-κB (RANK) stimulates the proliferation of epithelial cells of the epidermo-pilosebaceous unit

• DOI: 10.1073/pnas.1013054108
• Publication Date: 2011-03-15T20:49:42Z
• Authors: Vincent Duheron; Estelle Hess; Monique Duval; Marion Decossas; Beatriz Castaneda; Jennifer E. Klöpper; Leonela Amoasii; Jean-Baptiste Bar...; Ifor R. Williams; Hideo Yagita; Josef Penninger; Yongwon Choi; Frédéric Lézot; Richard Groves; Ralf Paus; Christopher G. Mu...
• Keywords: 570; Epidermis -- cytology -- physiology; Nude; TRANCE; Mice, Nude; Mice, Transgenic; [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]; RANK Ligand -- genetics -- metabolism; Inbred C57BL; Transgenic; Mice; 03 medical and health sciences; NF-kappa B -- metabolism; [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]; Epithelial Cells -- cytology -- physiology; Stem Cells -- cytology -- physiology; Animals; Homeostasis; Osteoprotegerin -- genetics -- metabolism; Anagen; S100A8; Receptor Activator of Nuclear Factor-kappa B -- genetics -- metabolism; Cell Proliferation; 0303 health sciences; Receptor Activator of Nuclear Factor-kappa B; Stem Cells; RANK Ligand; NF-kappa B; Osteoprotegerin; 600; Epithelial Cells; Skin Transplantation; Mice, Inbred C57BL; Epidermal Cells; Hair Follicle -- cytology -- physiology; Epidermis; Biologie; Hair Follicle

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.