Abstract

Objectives

   The objectives of this study were to identify differentially expressed
   transcripts and gene pathways in the vertebral bone of pigs receiving
   very high doses of vitamin A supplementation. Prior studies have
   ascertained that excessive vitamin A intake exhibits
   compartment-specific effects in bone tissue; these include regulating
   mineralisation genes in cortical bone containing bone marrow. Due to
   vertebral bone containing bone marrow, the hypothesis was that vitamin
   A will upregulate genes and pathways within vertebral bone that will
   favour bone mineralisation.

Methods

   A total of 64 indoor UK pigs, fed standard commercial diets, were split
   into 8 groups (n = 8 per group) and received daily dosing of retinyl
   propionate (RP) (0 up to 10,000 µg RP/kg BW) for 17 weeks. Vertebral
   bone was sampled from the 13^th thoracic vertebrae and RNA was
   extracted. RNA from control pigs and pigs receiving 10,000 µg RP/kg BW
   was labelled and hybridised on an Agilent 4^*44k microarray. Genespring
   was used to identify differentially expressed transcripts, and
   Ingenuity Pathway Analysis (IPA) was applied to recognise gene pathways
   associated with vitamin A supplementation. qRT-PCR was then performed
   to confirm differential gene expression on selected biomarkers.
   Kruskal-Wallis test was used to determine significant changes in gene
   expression in response to vitamin A dose.

Results

   A total of 318 transcripts were observed to be differentially
   regulated > 2-fold in the vertebral bone of pigs receiving 10,000 µg
   RP/kg BW, 199 transcripts (62.6%) were observed to be upregulated
   (P < 0.05). Genes relating to Rho-GTPases and regulation of
   cytoskeletal dynamics, such as CDC42 and FLNA, persisted among
   canonical pathways (P < 0.05). qRT-PCR confirmed an 8.17-fold
   upregulation of FLNA in vertebral bone of pigs receiving 3000 µg RP/kg
   BW (P < 0.01), but no clear effect of treatment was observed on CDC42
   expression (P = 0.147).

Conclusions

   Due to its role in the regulation of cytoskeletal reorganisation, of
   which subsequently affects both bone formation and resorption, the
   results suggest that high vitamin A intake potentially influences bone
   metabolism through interacting with the Rho-GTPase pathway.

Funding Sources

   Bill and Melinda Gates Foundation.
     __________________________________________________________________

   Articles from Current Developments in Nutrition are provided here
   courtesy of American Society for Nutrition
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