Receptor activator of NF-κB (RANK) stimulates the proliferation of epithelial cells of the epidermo-pilosebaceous unit
Open Access
- 14 March 2011
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 108 (13), 5342-5347
- https://doi.org/10.1073/pnas.1013054108
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.Keywords
This publication has 56 references indexed in Scilit:
- Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancerNature, 2010
- Two distinct mechanisms underlie progesterone-induced proliferation in the mammary glandProceedings of the National Academy of Sciences of the United States of America, 2010
- Reciprocal Requirements for EDA/EDAR/NF-κB and Wnt/β-Catenin Signaling Pathways in Hair Follicle InductionDevelopmental Cell, 2009
- A Two-Step Mechanism for Stem Cell Activation during Hair RegenerationCell Stem Cell, 2009
- Scratching the surface of skin developmentNature, 2007
- Epithelial Stem Cells: Turning over New LeavesCell, 2007
- Role of the vitamin D receptor in hair follicle biologyThe Journal of Steroid Biochemistry and Molecular Biology, 2007
- Ectodysplasin regulates the lymphotoxin-β pathway for hair differentiationProceedings of the National Academy of Sciences of the United States of America, 2006
- A Comprehensive Guide for the Accurate Classification of Murine Hair Follicles in Distinct Hair Cycle StagesJournal of Investigative Dermatology, 2001
- Out of Eden: Stem Cells and Their NichesScience, 2000