title: Ascorbic acid insufficiency induces the severe defect on bone formation via the down-regulation of osteocalcin production.
abstract: The L-gulono-γ-lactone oxidase gene (Gulo) encodes an essential enzyme in the synthesis of ascorbic acid from glucose. On the basis of previous findings of bone abnormalities in Gulo (-/-) mice under conditions of ascorbic acid insufficiency, we investigated the effect of ascorbic acid insufficiency on factors related to bone metabolism in Gulo (-/-) mice. Four groups of mice were raised for 4 weeks under differing conditions of ascorbic acid insufficiency, namely, wild type; ascorbic acid-sufficient Gulo (-/-) mice, 3-week ascorbic acid-insufficient Gulo (-/-) mice, and 4-week ascorbic acid-insufficient Gulo (-/-) mice. Four weeks of ascorbic acid insufficiency resulted in significant weight loss in Gulo (-/-) mice. Interestingly, average plasma osteocalcin levels were significantly decreased in Gulo (-/-) mice after 3 weeks of ascorbic acid insufficiency. In addition, the tibia weight in ascorbic acid-sufficient Gulo (-/-) mice was significantly higher than that in the other three groups. Moreover, significant decreases in trabecular bone volume near to the growth plate, as well as in trabecular bone attachment to the growth plate, were evident in 3- or 4-week ascorbic acid-insufficient Gulo (-/-). In summary, ascorbic acid insufficiency in Gulo (-/-) mice results in severe defects in normal bone formation, which are closely related to a decrease in plasma osteocalcin levels.
authors.affiliation: Labratory of Vitamin C and Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea. ; Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Won
authors.initials: W
authors.lastname: Kim
authors.affiliation: Labratory of Vitamin C and Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Seyeon
authors.initials: S
authors.lastname: Bae
authors.affiliation: Labratory of Vitamin C and Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Labratory of Vitamin C and Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yejin
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Labratory of Vitamin C and Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Psychology, Boston College, Chestnut Hill, MA, USA.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Lim
authors.affiliation: Labratory of Vitamin C and Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hei Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Labratory of Vitamin C and Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jihyuk
authors.initials: J
authors.lastname: Lee
authors.affiliation: Labratory of Vitamin C and Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jiyea
authors.initials: J
authors.lastname: Choi
authors.affiliation: Labratory of Vitamin C and Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Mirim
authors.initials: M
authors.lastname: Jang
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Kyoung Eun
authors.initials: KE
authors.lastname: Lee
authors.affiliation: Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sun G
authors.initials: SG
authors.lastname: Chung
authors.affiliation: Labratory of Vitamin C and Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Hwang
authors.affiliation: Labratory of Vitamin C and Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Kang
authors.affiliation: Labratory of Vitamin C and Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Wang Jae
authors.initials: WJ
authors.lastname: Lee
keywords: Ascorbic acid; L-Gulonolactone oxidase; Osteocalcin; Osteogenesis