Retinoic acid effects on in vitro palatal fusion and WNT signaling
| Autor: | Laury Amelia Roa Fuentes, Marjon Bloemen, Carine EL Carels, Frank ADTG Wagener, Johannes W Von den Hoff |
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| Přispěvatelé: | RS: MERLN - Instructive Biomaterials Engineering (IBE), Division Instructive Biomaterials Eng |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
EXPRESSION
palate fusion Science & Technology GENES Palate MOLECULAR-MECHANISMS PROLIFERATION Tretinoin Wnt signaling BETA-CATENIN PATHWAY Mice Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10] DIFFERENTIATION MEDIAL EDGE EPITHELIUM Dentistry Oral Surgery & Medicine retinoic acid Animals EMBRYONIC STEM-CELLS General Dentistry Wnt Signaling Pathway Life Sciences & Biomedicine INDUCED CLEFT-PALATE bone formation |
| Zdroj: | European Journal of Oral Sciences, 130(6):e12899. Blackwell Munksgaard European Journal of Oral Sciences, 130, 6 European Journal of Oral Sciences, 130 |
| ISSN: | 0909-8836 |
| DOI: | 10.1111/eos.12899 |
| Popis: | 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. ispartof: EUROPEAN JOURNAL OF ORAL SCIENCES vol:130 issue:6 ispartof: location:England status: published |
| Databáze: | OpenAIRE |
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