Dietary and Serum Phosphorus Regulate Fibroblast Growth Factor 23 Expression and 1,25-Dihydroxyvitamin D Metabolism in Mice

Perwad, Farzana; Azam, Nasreen; Zhang, Martin Y. H.; Yamashita, Takefumi; Tenenhouse, Harriet S.; Portale, Anthony A.

doi:10.1210/en.2005-0777

Cited by 387 publications

(276 citation statements)

References 39 publications

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“…Because inorganic phosphate has been shown to induce Fgf23 expression in osteocyte-like IDG-SW3 cells (40), it is possible that the influx of phosphate from the diet may regulate circadian Fgf23 expression; however, previous in vivo studies failed to demonstrate an acute effect of dietary phosphate on FGF23 induction (41,42), making this concept unlikely to be operative. Despite the lack of an increase in FGF23 levels in response to an acute phosphate load, it has been well established that a chronic phosphate load causes elevations in FGF23 levels (43). Consistent with previous reports, we detected a significant increase in skeletal Fgf23 expression in mice fed a high phosphate diet, but this increase was not associated with sympathetic activation because the concomitant administration of PRO did not affect Fgf23 expression.…”

Section: Discussionsupporting

confidence: 90%

Sympathetic Activation Induces Skeletal Fgf23 Expression in a Circadian Rhythm-dependent Manner

Kawai

Kinoshita

Shimba

et al. 2014

Journal of Biological Chemistry

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Background:The mechanism whereby the circadian clock regulates phosphate metabolism remains elusive. Results: Fgf23 expression is regulated by the time of food intake which involves the alteration in circadian profile of sympathetic activity. Conclusion:The circadian network plays important roles in phosphate metabolism. Significance: The sympathetic regulation of Fgf23 expression may shed light on new regulatory networks that could be important for phosphate homeostasis.

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Section: Discussionsupporting

confidence: 90%

Sympathetic Activation Induces Skeletal Fgf23 Expression in a Circadian Rhythm-dependent Manner

Kawai

Kinoshita

Shimba

et al. 2014

Journal of Biological Chemistry

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“…Recently, dietary consumption of phosphate was shown to increase serum FGF23 level in both uremic rats and non-uremic mice (10)(11)(12). In healthy individuals, increased dietary phosphate load has been reported to increase the serum level of FGF23 (13)(14)(15)(16).…”

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confidence: 99%

Effect of Calcitriol on FGF23 Level in Healthy Adults and its Dependence on Phosphate Level

Georgiadou

Marketou

Trovas

et al. 2017

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Abstract. Aim: To evaluate the short-term effects of calcitriol and sevelamer hydrochloride on fibroblast growth factor-23 (FGF23) in humans and to determine whether the effect is direct or indirect through calcitriol-induced increased absorption of phosphorus from the intestine. Patients andFibroblast growth factor-23 (FGF23) is a circulating factor that plays an important role in the regulation of phosphate and vitamin D (1-3). FGF23 is produced by mature osteoblasts and osteocytes (2) and acts through FGF receptor-Klotho complexes in cell membranes. The kidney is the major target for FGF23; in the proximal renal tubule, FGF23 acts to promote phosphaturia by down-regulating the expression of luminal sodium-dependent phosphate transporters and to reduce synthesis of 1,25-dihydroxyvitamin D by downregulating 1a-hydroxylase and up-regulating 24-hydroxylase activity (4-6).Although the control of FGF23 production remains poorly understood, a complex interplay between systemic and local factors allows the coordination of bone buffering capacity with renal phosphate handling. The primary systemic factors that stimulate FGF23 secretion appear to be calcitriol and increased dietary phosphorus intake. Moreover the FGF23 level is directly correlated with serum parathyroid hormone (PTH), calcium, and phosphate level in uremic patients who are on maintenance hemodialysis (7-9).There is evidence that the plasma FGF23 level is regulated or affected by dietary phosphate. Recently, dietary consumption of phosphate was shown to increase serum FGF23 level in both uremic rats and non-uremic mice (10-12). In healthy individuals, increased dietary phosphate load has been reported to increase the serum level of FGF23 (13-16).In addition, calcitriol was shown to up-regulate serum FGF23 level in mice and in parathyroidectomized rats without a corresponding increase in serum phosphate level 145

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“…Nutritional studies have revealed that the dietary restriction of phosphate intake results in decreased plasma levels of PTH by direct or indirect effect of plasma PO 4 3-levels [2] and that there occurs a delayed or improved secondary hyper-parathyroidism independent of plasma levels of Ca 2? or calcitriol.…”

Section: Basic Conceptsmentioning

confidence: 99%

The Roles of Fibroblast Growth Factor (FGF)-23, α-Klotho and Furin Protease in Calcium and Phosphate Homeostasis : A Mini-Review

Mattoo

2013

Ind J Clin Biochem

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The roles of calcitonin, parathormone and calcitriol in the regulation of plasma calcium and phosphate are well-established. However, in autosomal-dominant hypophosphatemic rickety patients, studies have revealed normal plasma levels of calcium, associated with normal thyroid and parathyroid functions, but decreased levels of phosphate and calcitriol despite adequate reserves of vitamin D. Also, in tumoral calcinosis, persistent hyperphosphatemia with increased levels of 1,25(OH) 2 D 3 have been observed. These studies indicate the involvement of factors other than the ones already known. The first decade of this century/millennium has led to the discovery of the involvement of fibroblast growth factor-23, furin protease and a-klotho in the homeostasis of calcium and phosphate, which is the subject of this mini-review. Basic ConceptsThe roles of three hormones, namely, thyrocalcitonin, parathyroid hormone (PTH/parathormone) and calcitriol (1, 25-dihydroxy cholecalciferol/1,25(OH) 2 D 3 ) in the regulation of plasma calcium and phosphate are well established. For instance, post in-take of meal, dietary Ca 2? and PO 4 3-uptake/absorption in the intestines takes place; while Ca 2? uptake is promoted because of the increased in vivo population of calcium transporting and binding proteins caused by increased de novo synthesis induced by calcitriol, the phosphate uptake occurs due to the increased activity of the Na ? /PO 4 3-co-transporter-2b; both these processes being brought about by calcitriol hormone derived from its pre-pro-precursor, vitamin D. This increased uptake of these two minerals in the intestine leads to a tide in plasma which needs to be dissipated. Thyrocalcitonin is released by thyroid glands in response to this tide, which promotes mineralization of the soft bones by inhibiting osteoclastic activities on the one hand and promoting osteoblastic activity on the other hand, thereby normalizing plasma levels of Ca 2? and PO 4 3-. Whenever plasma Ca 2? decreases (hypocalcemia), parathormone (PTH) is released by parathyroid glands. This hormone acts in conjunction with calcitriol in two ways, (a) by promoting osteocytes to secrete sclerostin, which binds bone morphogenetic receptor, leading to inhibition of osteogenesis, while promoting osteoclastic activity [1], i.e. (i) active release of proteases, glycosidases and phosphatases which cause breakdown of proteoglycan mesh and release of covalently-bound phosphate (organic phosphate) from proteins (such as, osteogenin), (ii) increased release of H ? due to increased osteoclastic carbonic anhydrase and (iii) consequential release of hydroxyapatite from c-carboxy-glutamate residues of peptides/proteins and its dissociation under acidic conditions, leading to demineralization and release into plasma of large amounts of Ca 2? and PO 4 3-from soft regions of bones, thereby reversing the osteogenic processes induced by thyrocalcitonin, and (b) by selective reabsorption, in conjunction with calcitriol, of Ca 2? on the

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Dietary and Serum Phosphorus Regulate Fibroblast Growth Factor 23 Expression and 1,25-Dihydroxyvitamin D Metabolism in Mice

Cited by 387 publications

References 39 publications

Sympathetic Activation Induces Skeletal Fgf23 Expression in a Circadian Rhythm-dependent Manner

Sympathetic Activation Induces Skeletal Fgf23 Expression in a Circadian Rhythm-dependent Manner

Effect of Calcitriol on FGF23 Level in Healthy Adults and its Dependence on Phosphate Level

The Roles of Fibroblast Growth Factor (FGF)-23, α-Klotho and Furin Protease in Calcium and Phosphate Homeostasis : A Mini-Review

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