In Vitro Non-Genomic Effects of Calcifediol on Human Preosteoblastic Cells

Donati, Simone; Palmini, Gaia; Romagnoli, Cecilia; Aurilia, Cinzia; Miglietta, Francesca; Falsetti, Irene; Marini, Francesca; Zonefrati, Roberto; Galli, Gianna; Marcucci, Gemma; Iantomasi, Teresa; Brandi, Maria Luisa

doi:10.3390/nu13124227

Cited by 8 publications

(14 citation statements)

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“…There is now compelling evidence that 1α,25(OH) 2 D 3 affects the target cells through genomic pathways and membrane receptor-mediated rapid, non-genomic responses. This latter mechanism has also been described for virtually all the steroid molecules, such as aldosterone, testosterone, estrogens, and cortisol [ 16 , 49 , 69 ].…”

Section: Discussionmentioning

confidence: 88%

“…Recently, even the direct metabolic precursor of 1α,25(OH) 2 D 3 , named calcifediol, it has been revealed able to activate rapid, nontranscriptional actions, such as an acute and sustained rise in intracellular Ca 2+ levels, similarly to that observed with the biologically active form of vitamin D 3 [ 16 , 70 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, 25(OH)D 3 , for a considerable time deemed only a metabolic precursor of 1α,25-(OH) 2 D 3 , has been proved to be an agonist ligand of VDR and capable of initiating rapid, non-genomic actions [ 16 , 19 ].…”

Section: Rapid Non-genomic Steroid Actionsmentioning

confidence: 99%

“…Based on this interesting observation, our previous research article [ 16 ] aimed to evaluate whether this metabolite could initiate rapid, non-genomic pathways, such as an increase in intracellular Ca 2+ concentrations, in line with what was established for calcitriol. We observed for the first time that calcifediol produces a rapid increase in Ca 2+ levels in mesenchymal stem cells derived from human adipose tissue (hADMSCs), although at a higher concentration compared to those present in normal physiological conditions.…”

Section: 25(oh)d 3 -Mediated Rapid Non-genomic Act...mentioning

confidence: 99%

“…In recent years, calcitriol, as well as its direct precursor, calcifediol, have been shown to exert rapid non-genomic steroid actions, indicating a more complex mechanism responsible for the wide range of actions of vitamin D [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Rapid Nontranscriptional Effects of Calcifediol and Calcitriol

et al. 2022

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Classically, a secosteroid hormone, vitamin D, has been implicated in calcium and phosphate homeostasis and has been associated with the pathogenesis of rickets and osteomalacia in patients with severe nutritional vitamin D deficiency. The spectrum of known vitamin D-mediated effects has been expanded in recent years. However, the mechanisms of how exactly this hormone elicits its biological function are still not fully understood. The interaction of this metabolite with the vitamin D receptor (VDR) and, subsequently, with the vitamin D-responsive element in the region of specific target genes leading to the transcription of genes whose protein products are involved in the traditional function of calcitriol (known as genomic actions). Moreover, in addition to these transcription-dependent mechanisms, it has been recognized that the biologically active form of vitamin D3, as well as its immediate precursor metabolite, calcifediol, initiate rapid, non-genomic actions through the membrane receptors that are bound as described for other steroid hormones. So far, among the best candidates responsible for mediating rapid membrane response to vitamin D metabolites are membrane-associated VDR (VDRm) and protein disulfide isomerase family A member 3 (Pdia3). The purpose of this paper is to provide an overview of the rapid, non-genomic effects of calcifediol and calcitriol, whose elucidation could improve the understanding of the vitamin D3 endocrine system. This will contribute to a better recognition of the physiological acute functions of vitamin D3, and it could lead to the identification of novel therapeutic targets able to modulate these actions.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Rapid Non-genomic Steroid Actionsmentioning

confidence: 99%

Section: 25(oh)d 3 -Mediated Rapid Non-genomic Act...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rapid Nontranscriptional Effects of Calcifediol and Calcitriol

et al. 2022

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Calcifediol: a review of its pharmacological characteristics and clinical use in correcting vitamin D deficiency

2023

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Background In addition to the role of vitamin D in bone mineralization, calcium and phosphate homeostasis, and skeletal health, evidence suggests an association between vitamin D deficiency and a wide range of chronic conditions. This is of clinical concern given the substantial global prevalence of vitamin D deficiency. Vitamin D deficiency has traditionally been treated with vitamin D 3 (cholecalciferol) or vitamin D 2 (ergocalciferol). Calcifediol (25-hydroxyvitamin D 3 ) has recently become available more widely. Methods By means of targeted literature searches of PubMed, this narrative review overviews the physiological functions and metabolic pathways of vitamin D, examines the differences between calcifediol and vitamin D 3 , and highlights clinical trials conducted with calcifediol in patients with bone disease or other conditions. Results For supplemental use in the healthy population, calcifediol can be used at doses of up to 10 µg per day for children ≥ 11 years and adults and up to 5 µg/day in children 3−10 years. For therapeutic use of calcifediol under medical supervision, the dose, frequency and duration of treatment is determined according to serum 25(OH)D concentrations, condition, type of patient and comorbidities. Calcifediol differs pharmacokinetically from vitamin D 3 in several ways. It is independent of hepatic 25-hydroxylation and thus is one step closer in the metabolic pathway to active vitamin D. At comparable doses to vitamin D 3 , calcifediol achieves target serum 25(OH)D concentrations more rapidly and in contrast to vitamin D 3 , it has a predictable and linear dose-response curve irrespective of baseline serum 25(OH)D concentrations. The intestinal absorption of calcifediol is relatively preserved in patients with fat malabsorption and it is more hydrophilic than vitamin D 3 and thus is less prone to sequestration in adipose tissue. Conclusion Calcifediol is suitable for use in all patients with vitamin D deficiency and may be preferable to vitamin D 3 for patients with obesity, liver disease, malabsorption and those who require a rapid increase in 25(OH)D concentrations.

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