Vitamin D: calcium and bone homeostasis during evolution

Abstract

Vitamin D 3 is already found early in the evolution of life but essentially as inactive end products of the photochemical reaction of 7-dehydrocholestol with ultraviolet light B. A full vitamin D (refers to vitamin D 2 and D 3 ) endocrine system, characterized by a specific VDR (vitamin D receptor, member of the nuclear receptor family), specific vitamin D metabolizing CYP450 enzymes regulated by calciotropic hormones and a dedicated plasma transport-protein is only found in vertebrates. In the earliest vertebrates (lamprey), vitamin D metabolism and VDR may well have originated from a duplication of a common PRX/VDR ancestor gene as part of a xenobiotic detoxification pathway. The vitamin D endocrine system, however, subsequently became an important regulator of calcium supply for an extensive calcified skeleton. Vitamin D is essential for normal calcium and bone homeostasis as shown by rickets in vitamin D-deficient growing amphibians, reptiles, birds and mammals. From amphibians onward, bone is gradually more dynamic with regulated bone resorption, mainly by combined action of PTH and 1a, (1,25(OH) 2 D 3 ) on the generation and function of multinucleated osteoclasts. Therefore, bone functions as a large internal calcium reservoir, under the control of osteoclasts. Osteocytes also display a remarkable spectrum of activities, including mechanical sensing and regulating mineral homeostasis, but also have an important role in global nutritional and energy homeostasis. Mineralization from reptiles onward is under the control of well-regulated SIBLING proteins and associated enzymes, nearly all under the control of 1,25(OH) 2 D 3 . The vitamin D story thus started as inert molecule but gained an essential role for calcium and bone homeostasis in terrestrial animals to cope with the challenge of higher gravity and calcium-poor environment.

A Multidisciplinary Approach in the Treatment of Fractures of the Proximal Femur on the Background of Senile Osteoporosis

“…При ведении пациентов с пере-ломами проксимального отдела бедренной кости в стар-ческом возрасте на фоне ОП и ОПН необходимо назна-чение препаратов кальция, как одного из основных компонентов коррекции деминерализации кости. Уни-кальность кальция в строительной функции костной ткани и регуляции ее процессов показана во многих экспериментальных и клинических исследованиях [47][48][49]. Уровень кальциемии является строгой константой [50].…”

Synthesis of 24,24-Difluoro-1,3-<i>cis</i>-25-dihydroxy-19-norvitamin D₃ Derivatives and Evaluation of Their Vitamin D Receptor-Binding Affinity

“…The extracts were washed with water and brine, dried over MgSO 4 , filtered and concentrated in vacuo. The residue was first eluted using 3% MeOH-CH 2 Cl 2 on a silica gel column, and then again purified on a preparative TLC plate using 5% MeOH-CH 2 Cl 2 as the mobile phase to give 6b (6.1 mg, 64% 3 , and their derivatives 5a, b, 6a and b for VDR was examined using a nuclear receptor cofactor assay system (Enbio RCAS for VDR, EnBioTec Laboratory) according to the manufacturer's instructions. First, the kit components were brought down at room temperature.…”

“…Recently, DeLuca and colleagues reported 24,24-difluoro-1α,25-(OH) 2 -19-norvitamin D 3 (4), which showed stronger vitamin D receptor (VDR) binding affinity than compound 2 and promoted bone formation more efficiently. 13) Thus, although 24-difluoro substitution has little effect on the biological potency of the natural hormone (2), it does alter the biological activity profile of 1α,25-(OH) 2 -19-norvitamin D 3 (3).…”

“…1; also known as calcitriol) is the active hormonal form of vitamin D 3 (1); it regulates calcium and phosphorus homeostasis and exhibits potent antiproliferative activity. [1][2][3][4] Its activity is regulated by the cytochrome oxidase P450 family member CYP24A1, which oxidizes 2 at the C24 and C23 positions to afford biologically inactive, side-chain-truncated, water-soluble end products. [5][6][7] However, the metabolic stability of 2 can be increased by substitution of side-chain hydrogen with fluorine, which is very similar in size to hydrogen, but has different chemical bonding properties.…”

Effects of 1α,25-Dihydroxyvitamin D₃ on Intestinal Absorption and Disposition of Adefovir Dipivoxil and Its Metabolite, Adefovir, in Rats

“…4) During the past decades, significant physiological roles of VDR in calcium and bone homeostasis have been well established. 5) However, it is increasingly recognized that VDR is also crucial in the regulation of drug transporters, and 1,25(OH) 2 D 3 can lead to VDR-mediated changes in target genes of drug transporters. [6][7][8][9][10] Since VDR is abundantly expressed in the intestine, 11) the effects of 1,25(OH) 2 D 3 (i.e., VDR activation) on the expression of intestinal drug transporters are frequently investigated.…”