This proposal is concerned with the effect of hormones, particularly insulin and l,25-dihydroxyvitamin D3 (l,25-(OH)2D3) on bone collegen metabolism. Our understanding of the mechanisms by which these hormones alter collagen synthesis and degratation is limited. Insulin markedly stimulates collagen synthesis in bone organ culture. The fact that diabetics appear to have bone abnormalities associated with a defect in bone formation suggests that insulin has an important role in matrix production in vivo. In bone organ culture l,25-(OH)2D3 decreases collagen synthesis; yet in vitamin D-deficient rats, vitamin D increases collagen synthesis. Thus, the control of matrix synthesis by l,25-(OH)2D3 is complex and probably depends on the vitamin D status of the animal. The goals of this study are to determine the sites at which insulin alters collagen synthesis in fetal rat hone and then to develop a model of diabetes in the rat to determine the effect of insulin-deficiency on bone collagen metabolism and structure. I will also examine the effects of l,25-(OH)2D3 on collagen synthesis in bone from vitamin D-deficient rat pups. Finally, I will characterize colonal cell lines from a rat osteosarcoma for their capacity to synthesize collagen so that these cells may be used as a possible model to study the effect of hormones on bone collagen metabolism. In these experiments, collagen synthesis is assessed by the incorporation of radiolabeled proline into collagen and by the formation of radiolabeled hydroxproline. Collagen degradation is measured by the formation of dialyzable radiolabeled hydroxyproline and hydroxylysine. Ultimately, these studies may give us a better understanding of the mechanisms by which hormones regulate collagen metabolism in bone.
