The effect of ascorbic acid deficiency on bone formation in Gulo knock out mice

ascorbic acid;vitamin C;Gulo;osteocalcin;bone formation

의과대학 의학과 ;

University:서울대학교 대학원

关键词: ascorbic acid;    vitamin C;    Gulo;    osteocalcin;    bone formation;   

Others  :  http://s-space.snu.ac.kr/bitstream/10371/132517/1/000000005429.pdf

美国|英语

来源: Seoul National University Open Repository

【 摘 要 】

L-gulono-γ-lactone oxidase (Gulo) is an essential enzyme in the synthesis of ascorbic acid from glucose. It is known that gulo is mutated in humans and certain primates. Gulo (-/-) mice are a useful animal model of human scurvy when they are raised under an ascorbic acid-deficient condition, since Gulo (-/-) mice have a defect in the expression of the gulo gene. Based on previous findings on bone abnormalities, including multiple chondrocostal junction fractures in Gulo (-/-) mice upon ascorbic acid insufficiency, the specific factors at work are investigated on the present study. At 4 weeks after ascorbic acid withdrawal, a definite loss of weight was found in ascorbic acid-insufficient Gulo (-/-) mice. Interestingly, the plasma level of osteocalcin, which is secreted solely by osteoblasts and is thought to play a role in the metabolic regulation of bone, was dramatically decreased in ascorbic acid-insufficient Gulo (-/-) mice 3 weeks after ascorbic acid withdrawal. In addition, it was no longer detected at 4 weeks after ascorbic acid withdrawal. The tibia weight of the ascorbic acid-sufficient Gulo (-/-) mice was significantly higher than the other three groups. The trabecular bone volume was decreased near the growth plate. Moreover, we found a significant decrease in the trabecular bone attachment to the growth plate in ascorbic acid-insufficient Gulo (-/-) mice at 3 or 4 weeks after ascorbic acid withdrawal. Taken together, there are severe defects in normal bone formation as the result of ascorbic acid insufficiency, and this effect is closely related to a decrease in the osteocalcin level.