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Publication : Epithelium-Derived Wnt Ligands Are Essential for Maintenance of Underlying Digit Bone.

First Author  Takeo M Year  2016
Journal  J Invest Dermatol Volume  136
Issue  7 Pages  1355-1363
PubMed ID  27021406 Mgi Jnum  J:233600
Mgi Id  MGI:5787700 Doi  10.1016/j.jid.2016.03.018
Citation  Takeo M, et al. (2016) Epithelium-Derived Wnt Ligands Are Essential for Maintenance of Underlying Digit Bone. J Invest Dermatol 136(7):1355-63
abstractText  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 beta-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 beta-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/beta-catenin signaling is critical for this interaction.
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