Abstract

Calvarial thinning and skull bone defects have been reported in infants with hypervitaminosis A. These findings have also been described in humans, mice and zebrafish with loss-of-function mutations in the enzyme CYP26B1 that degrades retinoic acid (RA), the active metabolite of vitamin A, indicating that these effects are indeed caused by too high levels of vitamin A and that evolutionary conserved mechanisms are involved. To explore these mechanisms, we have fed young mice excessive doses of vitamin A for one week and then analyzed the skull bones using micro computed tomography, histomorphometry, histology and immunohistochemistry. In addition, we have examined the effect of RA on gene expression in osteoblasts in vitro. Compared to a standard diet, a high dietary intake of vitamin A resulted in a rapid and significant reduction in calvarial bone density and suture diastasis. The bone formation rate was almost halved. There was also increased staining of tartrate resistant acid phosphatase in osteocytes and an increased perilacunar matrix area, indicating osteocytic osteolysis. Consistent with this, RA induced genes associated with bone degradation in osteoblasts in vitro. Moreover, and in contrast to other known bone resorption stimulators, vitamin A induced osteoclastic bone resorption on the endocranial surfaces.

Published in

PLoS ONE
2017, Volume: 12, number: 4, article number: e0176217
Publisher: PUBLIC LIBRARY SCIENCE

SLU Authors

• Pejler, Gunnar

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    
  • Uppsala University

UKÄ Subject classification

Biomaterials Science


Publication identifier

DOI: https://doi.org/10.1371/journal.pone.0176217

Permanent link to this page (URI)

https://res.slu.se/id/publ/82738