Evidence map›Paper›PMID 35716278›Full record

ArticleOrthodontics & craniofacial research2023

Excess vitamin a might contribute to submucous clefting by inhibiting WNT-mediated bone formation.

Charlotte Lucienne Jacqueline Maria Krutzen, Laury A Roa, Marjon Bloemen, Johannes W Von den Hoff

Open access · hybridAbstract read
In one paragraph

Article in Orthodontics & craniofacial research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Review
  3. Role of vitamins in the development and treatment of osteoporosis (Review).International journal of molecular medicine · 2025
    Review
  4. Article
  5. Observational
  6. Role of vitamins beyond vitamin DInternational journal of molecular medicine · 2024
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Charlotte Lucienne Jacqueline Maria KrutzenDepartment of Dentistry - Orthodontics and Craniofacial Biology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
Laury A RoaDepartment of Dentistry - Orthodontics and Craniofacial Biology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
Marjon BloemenDepartment of Dentistry - Orthodontics and Craniofacial Biology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
Johannes W Von den HoffDepartment of Dentistry - Orthodontics and Craniofacial Biology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.ORCID https://orcid.org/0000-0002-1616-1576
Radboud University Nijmegen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesCleft lip and/or palate (CLP) is a common craniofacial birth defect caused by genetic as well as environmental factors. The phenotypic spectrum of CLP also includes submucous clefts with a defect in the palatal bone. To elucidate the contribution of vitamin A, we evaluated the effects of the vitamin A metabolite all-trans retinoic acid (ATRA) on the osteogenic differentiation and mineralization of mouse embryonic palatal mesenchymal cells (MEPM). SETTING AND SAMPLE POPULATION: MEPM cells were isolated from the prefusion palates of E13 mouse embryos from three different litters. MATERIALS AND

methodsMEPM cells were cultured with and without 0.5 μM ATRA in osteogenic medium. Differentiation was analysed by the expression of osteogenic marker genes and alkaline phosphatase (ALP) activity after 1, 2, and 7 days. The expression of Wnt marker genes was also analysed. Mineralization was assessed by alizarin red staining after 7, 14, 21, and 28 days.

resultsThe bone marker genes Sp7, Runx2, Alpl, and Col1a1 were inhibited 10% ± 2%, 59% ± 7%, 79% ± 12% and 57% ± 20% (P < .05) at day 7. ALP activity was inhibited at days 1 and 7 by 35 ± 0% (P < .05) and 23 ± 6% (P < .001). ATRA also inhibited mineralization at 3 and 4 weeks. Finally, expression of the universal Wnt marker gene Axin2 was strongly reduced, by 31 ± 18% (P < .001), at day 7.

conclusionOur data indicate that ATRA (vitamin A) inhibits bone formation by reducing Wnt signalling. This might contribute to the molecular aetiology of submucous clefting.

Indexed as

Cleft LipCleft PalateAnimalsCell DifferentiationCells, CulturedMiceOsteogenesisTretinoinVitamin AWnt ProteinsTretinoinVitamin AWnt Proteinsmineralizationmouse embryonic palatal mesenchymal cellsosteoblast differentiationretinoic acidWNT signalling

Identifiers

PMID35716278
PMCPMC10084165
OpenAlexW4283074751

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.