Vitamin D

Biochemistry, nutrition and roles (vitamin D and bone)

Sadaoki Sakai, Yoshiteru Miyauchi, Yoshiaki Toyama, Takeshi Miyamoto

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Vitamin D was identified as a curative treatment for rickets, a human disease causing bone abnormalities. Sunbathing was known to be effective for rickets treatment, and vitamin D was isolated as a factor activated by UV irradiation. Indeed, UV irradiation is required to convert the active form of Vitamin D, 1α, 25-dihydroxyvitamin D3 (1α,25(OH)2D3), from pro-vitamin D. Since 1α,25(OH)2D3 is required to maintain bone and mineral homeostasis, the ingestion of Pro-vitamin D from diet is also important for bone homeostasis. Shorter sunlight exposure or reduced pro-vitamin D intake causes rickets. Basically, 1 α,25(OH)2D3 is synthesized by metabolic conversions in the liver and kidney, and can bind to the vitamin D receptor (VDR) to express biological activities through modulating transcription of target genes. Functional deficiency of the 1 α,25(OH)2D3 metabolic enzyme and the VDR by gene mutations also results in vitamin D-dependent rickets. 1 α,25(OH)2D3 or its analogs have been used for treatment of renal bone disease and hyperparathyroidism, and later used for osteoporosis treatment as well. Osteoporosis, a disease demonstrating decreased bone mineral density (BMD) and loss of bone strength due to excessive bone resorption, has been treated with 1α,25(OH)2D3 and its cognate analogs. Treatment with active vitamin D3 analogs is reportedly beneficial to correct abnormalities in mineral and bone metabolism in experimental animal models as well as in humans. Administration of active vitamin D analogs in ovariectomized (OVX) animals, a model for postmenopausal osteoporosis, reduces osteoclast number and bone resorption, thereby increasing BMD and bone strength. However, 1 α,25(OH)2D3 induces differentiation of osteoclasts, bone resorbing cells, in a co-culture of osteoclast precursor cells and osteoblastic cells in vitro. Treatment with 1α,25(OH)2D3 upregulates the expression of receptor activator of nuclear factor κ-B ligand (RANKL), an essential transmembrane ligand for osteoclastogenesis, while it downregulates osteoprotegerin (OPG), a decoy receptor of RANKL in osteoblasts, and that stimulates osteoclastogenesis in a coculture system. These discrepancies of in vivo and in vitro data make it difficult to understand the mechanisms underlying vitamin D3 action on bone. Recent advances showed that 1α,25(OH)2D3 directly acts on the osteoclast precursor cells, and downregulates c-Fos protein, an essential transcription factor for osteoclast differentiation, or induces IFN-β, a strong inhibitor of osteoclast differentiation, thereby inhibiting osteoclast differentiation. These findings, at least in part, elucidate the anti-bone resorbing mechanisms of active vitamin D analogs in osteoporotic patients. In this context, the role of Vitamin D on bone metabolism including recent findings is discussed.

Original languageEnglish
Title of host publicationVitamin D: Biochemistry, Nutrition and Roles
PublisherNova Science Publishers, Inc.
Pages105-128
Number of pages24
ISBN (Print)9781616682736
Publication statusPublished - 2011

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Vitamin D
Biochemistry
Osteoclasts
Bone and Bones
Rickets
Calcitriol Receptors
Cholecalciferol
Bone Diseases
Bone Resorption
Coculture Techniques
Osteogenesis
Bone Density
Osteoporosis
Minerals
Sunbathing
Homeostasis
Down-Regulation
Animal Models
Proto-Oncogene Proteins c-fos
Ligands

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Sakai, S., Miyauchi, Y., Toyama, Y., & Miyamoto, T. (2011). Vitamin D: Biochemistry, nutrition and roles (vitamin D and bone). In Vitamin D: Biochemistry, Nutrition and Roles (pp. 105-128). Nova Science Publishers, Inc..

Vitamin D : Biochemistry, nutrition and roles (vitamin D and bone). / Sakai, Sadaoki; Miyauchi, Yoshiteru; Toyama, Yoshiaki; Miyamoto, Takeshi.

Vitamin D: Biochemistry, Nutrition and Roles. Nova Science Publishers, Inc., 2011. p. 105-128.

Research output: Chapter in Book/Report/Conference proceedingChapter

Sakai, S, Miyauchi, Y, Toyama, Y & Miyamoto, T 2011, Vitamin D: Biochemistry, nutrition and roles (vitamin D and bone). in Vitamin D: Biochemistry, Nutrition and Roles. Nova Science Publishers, Inc., pp. 105-128.
Sakai S, Miyauchi Y, Toyama Y, Miyamoto T. Vitamin D: Biochemistry, nutrition and roles (vitamin D and bone). In Vitamin D: Biochemistry, Nutrition and Roles. Nova Science Publishers, Inc. 2011. p. 105-128
Sakai, Sadaoki ; Miyauchi, Yoshiteru ; Toyama, Yoshiaki ; Miyamoto, Takeshi. / Vitamin D : Biochemistry, nutrition and roles (vitamin D and bone). Vitamin D: Biochemistry, Nutrition and Roles. Nova Science Publishers, Inc., 2011. pp. 105-128
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