Retinoic acid effects on in vitro palatal fusion and WNT signaling.

Eur J Oral Sci

Department of Orthodontics and Craniofacial Biology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.

Published: December 2022

AI Article Synopsis

  • Retinoic acid, an active form of vitamin A, is crucial for embryonic development, but excess levels can disrupt palate formation, leading to cleft palates in mice.
  • In a study analyzing mouse embryo palate cultures, retinoic acid treatment showed a significant decrease in palate fusion rates and altered key signaling pathways, particularly increasing WNT signaling.
  • The findings indicated that retinoic acid interferes with bone formation and palate development by enhancing WNT pathway activity while downregulating genes involved in bone formation.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10092745PMC
http://dx.doi.org/10.1111/eos.12899DOI Listing

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