Vitamin D Regulation of Type I Collagen Expression in Bone

Publisher Summary

Vitamin D has multiple functions in humans and animals. It is the best known as a nutrient required for adequate growth and mineralization of bone. Some of the most well-recognized features of vitamin D deficiency are undermineralized bone in children (rickets) and adults (osteomalacia), a reduction in bone matrix formation and mineralization and an alteration in the pattern of collagen crosslinking. Calcium deficiency also decreases bone formation and mineralization in rats. Defective bone formation and mineralization in vitamin-D-deficient rats can be largely corrected by the administration of calcium and phosphate, suggesting that the trophic effect of vitamin D on the skeleton may be due to its ability to stimulate intestinal calcium absorption. Accordingly, preservation of mineral homeostasis in vitamin D receptor- (VDR) null mice reverses the abnormal skeletal phenotype (including excessive osteoid production) seen in animals, suggesting that a key effect of vitamin D on bone mineralization may be due to its stimulation of intestinal calcium absorption. The effect of 1,25(OH)₂D₃ on collagen expression, either inhibitory or stimulatory, may depend in part on in vitro culture conditions such as cell density, the timing, and concentration of 1,25(OH)₂D₃. When serum calcium and phosphate are low, parathyroid hormone increases the synthesis of 1,25(OH)₂D₃. Both hormones increase bone resorption to increase the supply of calcium and phosphate for soft tissues. At the same time, 1,25(OH)₂D₃ may stimulate the differentiation of early osteoprogenitors to differentiation into a new cohort of osteoblasts that would initiate the phase of coupled formation.