Changes in bone metabolic parameters following oral calcium supplementation in an adult patient with vitamin D-dependent rickets type 2A

Kinoshita, Yuka; Ito, Nobuaki; Makita, Noriko; Nangaku, Masaomi; Fukumoto, Seiji

doi:10.1507/endocrj.ej16-0583

Cited by 5 publications

(3 citation statements)

References 50 publications

(37 reference statements)

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“…This increase was mostly attributed to increased Fgf23 expression in the bone. When UMR106 osteosarcoma cells were treated with vitamin D, a significant upregulation of Ffg23 expression was found after 4 h. Addition of actinomycin D, a gene transcription inhibitor, completely abolished the upregulation of Fgf23, thus showing that increased Fgf23 expression by 1,25(OH) This is also showed in patients with inactivating mutations in the VDR gene who have lower FGF23 serum levels (47). When 1,25 (OH) 2 D 3 binds to the VDR, it heterodimerizes with the retinoid X receptors (RXR), this complex can bind to the vitamin D response element (VDRE) in the promotor of target genes ( Figure 2) It is important to note that some of the work on Fgf23 regulation by 1,25(OH) 2 D 3 is performed using mice and rats, which are both nocturnal species.…”

Section: Circulating Fgf23 Regulators 125-dihydroxyvitamin Dmentioning

confidence: 78%

Upstream Regulators of Fibroblast Growth Factor 23

2021

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Fibroblast growth factor 23 (FGF23) has been described as an important regulator of mineral homeostasis, but has lately also been linked to iron deficiency, inflammation, and erythropoiesis. FGF23 is essential for the maintenance of phosphate homeostasis in the body and activating mutations in the gene itself or inactivating mutations in its upstream regulators can result in severe chronic hypophosphatemia, where an unbalanced mineral homeostasis often leads to rickets in children and osteomalacia in adults. FGF23 can be regulated by changes in transcriptional activity or by changes at the post-translational level. The balance between O-glycosylation and phosphorylation is an important determinant of how much active intact or inactive cleaved FGF23 will be released in the circulation. In the past years, it has become evident that iron deficiency and inflammation regulate FGF23 in a way that is not associated with its classical role in mineral metabolism. These conditions will not only result in an upregulation of FGF23 transcription, but also in increased cleavage, leaving the levels of active intact FGF23 unchanged. The exact mechanisms behind and function of this process are still unclear. However, a deeper understanding of FGF23 regulation in both the classical and non-classical way is important to develop better treatment options for diseases associated with disturbed FGF23 biology. In this review, we describe how the currently known upstream regulators of FGF23 change FGF23 transcription and affect its post-translational modifications at the molecular level.

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Section: Circulating Fgf23 Regulators 125-dihydroxyvitamin Dmentioning

confidence: 78%

Upstream Regulators of Fibroblast Growth Factor 23

2021

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“…Vitamin D-dependent rickets type 2A is an inherited autosomal recessive type of rickets characterized by resistance to 1,25(OH) 2 D. 46 It is also called vitamin D-resistant rickets, hereditary 1,25(OH) 2 D-resistant rickets, rickets-alopecia syndrome, hereditary hypocalcemic vitamin D-resistant rickets, and pseudovitamin D-deficiency type 2A. 7 , 26 …”

Section: Vitamin D-dependent Rickets Type 1b (Mim 600081)mentioning

confidence: 99%

Genetic Forms of Calciopenic Rickets

Donmez¹,

Türkyılmaz²,

Çayır³

2023

Eurasian J Med

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Rickets is a disease involving calcium and phosphate balance disturbances in the pediatric population. A series of hereditary disorders known as vitamin D-dependent rickets are defined as early-onset rickets resulting from either an insufficient response to active vitamin D or an inability to maintain adequate levels of the active forms of vitamin D. According to the age at onset and the pathophysiology of the disease, various clinical signs including growth failure, limb bowing, and joint enlargement may be present. Vitamin D-dependent rickets type 1A, type 1B, type 2A, type 2B, and type 3 are classified as genetic forms. Further studies are crucial for the development of targeted therapies and future mutation-specific therapies.

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“…1,25(OH) 2 D increases FGF23 levels in vivo and in vitro by upregulating Fgf23 transcription (33)(34)(35)(36)(37). Conversely, VDR-knockout (Vdr -/-) mice have low serum FGF23 levels, which can be increased by feeding a rescue diet high in phosphate and calcium (38)(39)(40)(41).…”

Section: Introductionmentioning

confidence: 99%

1,25-Dihydroxyvitamin D3 regulates furin-mediated FGF23 cleavage

Xie,

Bastepe,

Zhou

et al. 2023

JCI Insight

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Intact fibroblast growth factor 23 (iFGF23) is a phosphaturic hormone that is cleaved by furin into N-terminal and C-terminal fragments. Several studies have implicated vitamin D in regulating furin in infections. Thus, we investigated the effect of 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D] and the vitamin D receptor (VDR) on furin-mediated iFGF23 cleavage. Mice lacking VDR ( Vdr –/– ) had a 25-fold increase in iFGF23 cleavage, with increased furin levels and activity compared with wild-type (WT) littermates. Inhibition of furin activity blocked the increase in iFGF23 cleavage in Vdr –/– animals and in a Vdr -knockdown osteocyte OCY454 cell line. Chromatin immunoprecipitation revealed VDR binding to DNA upstream of the Furin gene, with more transcription in the absence of VDR. In WT mice, furin inhibition reduced iFGF23 cleavage, increased iFGF23, and reduced serum phosphate levels. Similarly, 1,25(OH) 2 D reduced furin activity, decreased iFGF23 cleavage, and increased total FGF23. In a post hoc analysis of a randomized clinical trial, we found that ergocalciferol treatment, which increased serum 1,25(OH) 2 D, significantly decreased serum furin activity and iFGF23 cleavage, compared with placebo. Thus, 1,25(OH) 2 D inhibits iFGF23 cleavage via VDR-mediated suppression of Furin expression, thereby providing a mechanism by which vitamin D can augment phosphaturic iFGF23 levels.

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Changes in bone metabolic parameters following oral calcium supplementation in an adult patient with vitamin D-dependent rickets type 2A

Cited by 5 publications

References 50 publications

Upstream Regulators of Fibroblast Growth Factor 23

Upstream Regulators of Fibroblast Growth Factor 23

Genetic Forms of Calciopenic Rickets

1,25-Dihydroxyvitamin D3 regulates furin-mediated FGF23 cleavage

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