Calciprotein particles regulate fibroblast growth factor-23 expression in osteoblasts

Akiyama, Kenichi; Miura, Yutaka; Hayashi, Hirosaka; Sakata, Asuka; Matsumura, Yoshitaka; Kojima, Masaki; Tsuchiya, Ken; Nitta, Kosaku; Shiizaki, Kazuhiro; Kurosu, Hiroshi; Kuro‐o, Makoto

doi:10.1016/j.kint.2019.10.019

Cited by 83 publications

(97 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A study in rats showed that increased Fgf23 transcription in response to high dietary phosphate is only possible when serum calcium levels are also high (84). This is in agreement with another study showing that it is not the increase of phosphate itself that increases Fgf23 transcription, but rather the formation of calciprotein particles (CCPs) (85). CCPs are colloidal nanoparticles that consist of calcium and phosphate circulating in the blood and are potentially harmful as they contribute to vascular calcification.…”

Section: Calciumsupporting

confidence: 68%

Upstream Regulators of Fibroblast Growth Factor 23

2021

View full text Add to dashboard Cite

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.

show abstract

Section: Calciumsupporting

confidence: 68%

Upstream Regulators of Fibroblast Growth Factor 23

2021

View full text Add to dashboard Cite

show abstract

“…Next, we incubated the mixture for 24 h at 37 °C and then centrifuged it at 16,000 × g for 2 h. After removing the supernatant, we suspended the precipitated CPPs with the same amount (25 mL) of DMEM/F-12 containing 10% FBS to make 1 × CPP, or one-fifth of the initial amount (5 mL), to make 5 × CPP. The total calcium and phosphorus content in 1 × CPP was determined by ICP-MS Nexion 2000 as previously described 54 . 1 × CPP contained 174.8 μg calcium/mL (4.36 mM) with the standard error of mean ± 3.0 and 105.2 μg phosphorus/mL (3.40 mM) with the standard error of mean ± 2.9.…”

Section: Cpp Preparationmentioning

confidence: 99%

Calciprotein particle-induced cytotoxicity via lysosomal dysfunction and altered cholesterol distribution in renal epithelial HK-2 cells

Kunishige

Mizoguchi

Tsubouchi

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Dietary phosphate overload induces chronic kidney disease (CKD), and calciprotein particles (CPPs), a form of nanoparticle comprising calcium phosphate and serum proteins, has been proposed to cause renal toxicity. However, the mechanism of CPP cytotoxicity in renal tubular cells is unknown. Here we show that in renal proximal tubular epithelial HK-2 cells, endocytosed CPPs accumulate in late endosomes/lysosomes (LELs) and increase their luminal pH by ~ 1.0 unit. This results in a decrease in lysosomal hydrolase activity and autophagic flux blockage without lysosomal rupture and reactive oxygen species generation. CPP treatment led to vulnerability to H2O2-induced oxidative stress and plasma membrane injury, probably because of autophagic flux blockage and decreased plasma membrane cholesterol, respectively. CPP-induced disruption of lysosomal homeostasis, autophagy flux and plasma membrane integrity might trigger a vicious cycle, leading to progressive nephron loss.

show abstract

“…And most recently, Akiyama et al determined the hydrodynamic radii of CPPs in cell culture by small angle X-ray scattering (SAXS), from which they derived the size and shape of CPPs [19]. However, it remains a challenging task to acquire direct structural information of the protein-bound calcium phosphate, owing to the crystallizing propensity of the calcium phosphate clusters and amorphous phase.…”

Section: Introductionmentioning

confidence: 99%

Protein-bound calcium phosphate in uremic rat serum: a quantitative study

et al. 2020

View full text Add to dashboard Cite

Protein-bound calcium (prCa) constitutes about 40% of serum total calcium, in which albumin is the most dominant protein. Given the chemical interaction between calcium and phosphate (Pi), the increased serum Pi in chronic kidney disease may cause changes in the composition and structure of the prCa fraction. Here, we report the phosphate binding on the protein-bound calcium in uremic rat serum. Using adenine-fed rats as a uremic model, we determined the levels of calcium and phosphate fractions in rat serum by ultrafiltration, and found that the level of protein-bound phosphate (prPi) in the uremic serum was markedly higher than in control. The elevated prPi level was comparable to the prCa level, consistent with the presence of protein-bound calcium phosphate pr(Ca)j-m(CaPi)m. We then confirmed its presence by ex vivo X-ray absorption near-edge structure spectroscopy, revealing the discrete state of the calcium phosphate clusters associated with protein. Finally, in a quantitative investigation using Ca-and Piboosted serum, we discovered the threshold concentration for the Pi binding on prCa, and determined the binding constant. The threshold, while preventing Pi from binding to prCa in normal condition, allows excess Pi to do so. The protein-bound calcium phosphate could act as a link between the metabolism of serum proteins and the homeostasis of phosphate and calcium, and it deserves further investigation whether the molar ratio of (prPi/prCa)100% may serve as a serum index of the vascular calcification status in chronic kidney disease.

show abstract

Calciprotein particles regulate fibroblast growth factor-23 expression in osteoblasts

Cited by 83 publications

References 25 publications

Upstream Regulators of Fibroblast Growth Factor 23

Upstream Regulators of Fibroblast Growth Factor 23

Calciprotein particle-induced cytotoxicity via lysosomal dysfunction and altered cholesterol distribution in renal epithelial HK-2 cells

Protein-bound calcium phosphate in uremic rat serum: a quantitative study

Contact Info

Product

Resources

About