title: The Roles and Mechanisms of Actions of Vitamin C in Bone: New Developments.
abstract: Vitamin C is an important antioxidant and cofactor that is involved in the regulation of development, function, and maintenance of several cell types in the body. Deficiencies in vitamin C can lead to conditions such as scurvy, which, among other ailments, causes gingivia, bone pain, and impaired wound healing. This review examines the functional importance of vitamin C as it relates to the development and maintenance of bone tissues. Analysis of several epidemiological studies and genetic mouse models regarding the effect of vitamin C shows a positive effect on bone health. Overall, vitamin C exerts a positive effect on trabecular bone formation by influencing expression of bone matrix genes in osteoblasts. Recent studies on the molecular pathway for vitamin C actions that include direct effects of vitamin C on transcriptional regulation of target genes by influencing the activity of transcription factors and by epigenetic modification of key genes involved in skeletal development and maintenance are discussed. With an understanding of mechanisms involved in the uptake and metabolism of vitamin C and knowledge of precise molecular pathways for vitamin C actions in bone cells, it is possible that novel therapeutic strategies can be developed or existing therapies can be modified for the treatment of osteoporotic fractures.
authors.affiliation: Musculoskeletal Disease Center, Jerry L Pettis VA Medical Center, Loma Linda, CA, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Aghajanian
authors.affiliation: Musculoskeletal Disease Center, Jerry L Pettis VA Medical Center, Loma Linda, CA, USA.|Department of Medicine, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Hall
authors.affiliation: Musculoskeletal Disease Center, Jerry L Pettis VA Medical Center, Loma Linda, CA, USA.|Department of Orthopaedic Surgery, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Montri D
authors.initials: MD
authors.lastname: Wongworawat
authors.affiliation: Musculoskeletal Disease Center, Jerry L Pettis VA Medical Center, Loma Linda, CA, USA.|Department of Medicine, Loma Linda University, Loma Linda, CA, USA.|Department of Orthopaedic Surgery, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Subburaman
authors.initials: S
authors.lastname: Mohan
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000096:biosynthesis / Q000378:metabolism*; D001206:Ascorbic Acid Deficiency / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002356:Cartilage / Q000166:cytology; D004195:Disease Models, Animal; D006801:Humans; D008954:Models, Biological
chemical_list: D001205:Ascorbic Acid
keywords: BONE FRACTURE; ENDOCHONDRAL BONE FORMATION; EPIGENETICS; HYPOXIA-INDUCIBLE FACTORS; OSTEOBLASTS; OSTEOPOROSIS; PROLYL HYDROXYLASE DOMAIN-CONTAINING PROTEIN 2