Nutritionally induced cellular signals involved in the initiation of bone abnormalities in the hypovitaminosis D kyphotic pig model.

摘要

Skeletal unsoundness, ultimately leading to lameness, and human diseases associated with loss of bone integrity are continuing problems. Both lack sufficient models to study factors that initiate bone abnormalities. Most studies have focused on characteristics of the final lesion. Consequently, the contribution of different nutrients to the initiation of bone lesions is not completely understood which hampers early detection, prevention, and treatment. The approach by nutritionists and health professionals has often been to recommend excessive amounts of supplemental vitamin D (D), which may alleviate immediate issues, but long term effects in these situations remains unknown.;Results reported herein demonstrate our ability to reproduce the hypovitaminosis D kyphotic pig model through perturbations of sow and growing pig diets. Sow diets included 0 (-D), 325 (+D), or 1750 (++D) IU D3/kg throughout gestation and lactation. At weaning (3 wk) pigs were fed diets with 0 (-D) or 280 (+D) IU D3/kg and relatively minor modifications to dietary Ca and P to exacerbate responses to dietary D through the nursery phase.;Pigs produced by --D sows had an 11% reduction in growth (P < 0.05) and 25% reduction in bone mineral content (P < 0.05), regardless of nursery diet. Significant interactions between maternal and nursery diets were detected. Pigs produced by --D sows were at highest risk of developing kyphosis. Bone and soft tissue responses to maternal and nursery dietary D were not explained by serum or tissue 25-OH-D3 concentrations. Significant maternal and nursery diet effects on mRNA expression of genes involved in D homeostasis (1alpha-hydroxylase and 24-hydroxylase) and bone metabolism (matrix metalloproteinases and fibroblast growth factor 23) were evident.;Maternal dietary D carryover effects on soft tissue growth, skeletal mineralization, and expression of genes related to D metabolism and endochondral ossification were evident in young pigs. However, changes in serum and tissue 25-OH-D3 concentrations were not reflective of bone abnormalities. In future experiments we hope to characterize potential epigenetic effects of maternal dietary D through measurement of methylation patterns in response to supplemental D and to ultimately identify a biomarker for early detection of bone abnormalities prior to final lesion manifestation.