The role of vitamin A during bio-mineral tissue development in pigs

Abstract

Skeletal health is a critical determinant of animal health and welfare. Kyphosis is one such idiopathic skeletal disease that compromises the welfare of commercial pigs. Vitamin A regulates the expression of genes that define bone growth and development, and has been suggested to associate with kyphosis. This thesis aimed to establish the molecular basis of kyphosis, clarify vitamin A’s role on the expression of genes that regulate skeletal development, and to ascertain vitamin A’s role on gene expression in kyphotic pigs. The TGF-β signalling pathway was associated with kyphotic bone and cartilage tissues. This was due to bone and cartilage tissues showing associations with small-leucine rich proteoglycans, ASPN and DCN respectively, which regulate TGF- β signalling. Potential effects as a result of differential gene expression include reduced endochondral bone growth and deterioration of articular cartilage. The dose of vitamin A was observed to be a critical factor in the regulation of expression of skeletal genes within bone tissue. Genes related to the family of Rho-GTPases, which control cytoskeletal dynamics, were observed to be differentially regulated within the trabecular bone in response to vitamin A. In addition, vitamin A dose was observed to initially antagonise serum 25(OH) D, and upon full saturation of the liver with vitamin A, serum 25(OH) D was restored through, as of yet, unknown mechanisms. The gene GIT2, which associates with Rho-GTPases, was observed to be differentially downregulated within kyphotic trabecular bone, and showed a dose-response relationship with vitamin A supplementation. Furthermore, kyphotic pigs were indicated to have reduced vitamin D status. This research has outlined the molecular basis of kyphosis in pigs, and has indicated vitamin A and vitamin D drive the disease. The research also outlines the role of how excessive vitamin A controls the expression of genes that regulate bio-mineralisation in trabecular bone. The thesis has also offered novel insights into vitamin A’s potential role in regulating gene expression during kyphotic development.