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Retinoic acid effects on in vitro palatal fusion and WNT signaling
Author(s) -
Roa Fuentes Laury Amelia,
Bloemen Marjon,
Carels Carine EL,
Wagener Frank ADTG,
Von den Hoff Johannes W
Publication year - 2022
Publication title -
european journal of oral sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.802
H-Index - 93
eISSN - 1600-0722
pISSN - 0909-8836
DOI - 10.1111/eos.12899
Subject(s) - retinoic acid , wnt signaling pathway , axin2 , dkk1 , chemistry , tretinoin , microbiology and biotechnology , biology , signal transduction , medicine , biochemistry , gene
Retinoic acid is the main active vitamin A derivate and a key regulator of embryonic development. Excess of retinoic acid can disturb palate development in mice leading to cleft palate. WNT signaling is one of the main pathways in palate development. We evaluated the effects of retinoic acid on palate fusion and WNT signaling in in vitro explant cultures. Unfused palates from E13.5 mouse embryos were cultured for 4 days with 0.5 μM, 2 μM or without retinoic acid. Apoptosis, proliferation, WNT signaling and bone formation were analyzed by histology and quantitative PCR. Retinoic acid treatment with 0.5 and 2.0 μM reduced palate fusion from 84% (SD 6.8%) in the controls to 56% (SD 26%) and 16% (SD 19%), respectively. Additionally, 2 μM retinoic acid treatment increased Axin2 expression. Retinoic acid also increased the proliferation marker Pcna as well as the number of Ki‐67‐positive cells in the palate epithelium. At the same time, the WNT inhibitors Dkk1, Dkk3, Wif1 and Sfrp1 were downregulated at least two‐fold. Retinoic acid also down‐regulated Alpl and Col1a2 gene expression. Alkaline phosphatase (ALP) activity was notably reduced in the osteogenic areas of the retinoic acid‐ treated palates. Our data suggest that retinoic acid impairs palate fusion and bone formation by upregulation of WNT signaling.