title: Epithelium-Derived Wnt Ligands Are Essential for Maintenance of Underlying Digit Bone.
abstract: Clinically, many nail disorders accompany bone deformities, but whether the two defects are causally related is under debate. To investigate the potential interactions between the two tissue types, we analyzed epithelial-specific β-catenin-deficient mice, in which nail differentiation is abrogated. These mice showed regression of not only the nail plate but also of the underlying digit bone. Characterization of these bone defects revealed active bone resorption, which is suppressed by Wnt activation in osteoblast and osteoclast precursors. Furthermore, we found that Wntless expression, essential for Wnt ligand secretion, was lacking in the β-catenin-deficient nail epithelium and that genetic deletion of Wntless (Wls) in the nail epithelium led to the lack of Wnt activation in osteoblast and osteoclast precursors and subsequently led to defective regression of the underlying digit bone. Together, these data show that epithelial Wnt ligands can ultimately regulate Wnt signaling in osteoblast and osteoclast precursors, known to regulate bone homeostasis. These results reveal a critical role for the nail epithelium on the digit bone during homeostatic regeneration and show that Wnt/β-catenin signaling is critical for this interaction.
authors.affiliation: The Ronald O. Perelman Department of Dermatology, School of Medicine, New York University, New York, New York, USA; The Department of Cell Biology, School of Medicine, New York University, New York, New York, USA.
authors.forename: Makoto
authors.initials: M
authors.lastname: Takeo
authors.affiliation: The Ronald O. Perelman Department of Dermatology, School of Medicine, New York University, New York, New York, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Hale
authors.affiliation: The Ronald O. Perelman Department of Dermatology, School of Medicine, New York University, New York, New York, USA; The Department of Cell Biology, School of Medicine, New York University, New York, New York, USA. Electronic address: mayumi.ito@nyumc.org.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ito
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000473:pathology*; D002454:Cell Differentiation; D018920:Coculture Techniques; D004848:Epithelium / Q000378:metabolism / Q000473:pathology*; D005552:Forelimb / Q000473:pathology; D006706:Homeostasis; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D011995:Recombination, Genetic; D012038:Regeneration; D014034:Toes / Q000473:pathology*; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C495267:CTNNB1 protein, mouse; D008024:Ligands; D051153:Wnt Proteins; D051176:beta Catenin