The bone and the kidney

Mazzaferro, Sandro; Pasquali, Marzia; Pirrò, Giuliana; Rotondi, Silverio; Tartaglione, Lida

doi:10.1016/j.abb.2010.06.028

Cited by 28 publications

(13 citation statements)

References 116 publications

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“…In fact, PHEX protein stimulates FGF23 degradation [26] thus reducing its activity. By interacting with its co-receptor Klotho, FGF23 increases tubular phosphate excretion and inhibits 1,25D synthesis [27,28] with eventual well described clinical effects [8,29]. As a confirmation, Sclerostin knock-out mice have decreased FGF23 with elevated inorganic phosphate concentrations and increased 1,25D levels [26].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, also indirect effects of Sclerostin on mineral metabolism are envisaged, since Sclerostin can increase the activity of Fibroblast growth Factor 23 (FGF23), a bone protein with powerful phosphate and vitamin D regulating properties [7]. Thus, Sclerostin promises to become an important element of the bone-kidney axis represented up to now by FGF23 and its kidney-produced co-receptor Klotho [8]. For these reasons, recent clinical studies aim to evaluate Sclerostin as a new biomarker of bone disease specifically in chronic kidney disease (CKD).…”

Section: Introductionmentioning

confidence: 99%

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Interactions of sclerostin with FGF23, soluble klotho and vitamin D in renal transplantation

et al. 2017

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Relationships of Sclerostin, a bone anti-anabolic protein, with biomarkers of mineral bone disorders in chronic kidney disease are still unsettled, in particular in kidney transplant (KTR). In 80 KTR patients (31F/49M, 54.7±10.3 years) we studied the relationships of serum Sclerostin with eGFR, Calcium, Phosphate, Alkaline Phosphatase (AP), intact Parathyroid hormone (iPTH), soluble alpha-Klotho (sKlotho), intact Fibroblast Growth Factor 23 (iFGF23), 25-hydroxyvitamin D(25D) and 1,25-dihydroxyvitamin D (1,25D). Thirty healthy subjects (35.0±12.4 years, eGFR 109.1±14.1 ml /min/1,73m2) served as control for Sclerostin, iFGF23 and sKlotho. With a median eGFR of 46.3 mL/min/1.73m2 (IQR, 36.2–58.3) our KTR had median Sclerostin levels of 23.7 pmol/L (IQR: 20.8–32.8), not different from controls (26.6 pmol/L, IQR: 22.0–32.2; p = n.s). Sclerostin correlated negatively with AP (r = -.251; p = 0.023) and positively with iFGF23 (r = .227; p = 0.017) and 25D (r = .214; p = 0.025). Age-adjusted multiple regression analysis identified AP and 1,25D as negative and 25D and sKlotho as positive best predictors of Sclerostin. No correlation was evident with eGFR. The negative correlation with AP confirms the direct anti-anabolic role of Sclerostin. The associations either negative or positive with iFGF23, sKlotho, and vitamin D metabolites suggest also a modulatory role in mineral homeostasis. In particular, the associations with iFGF23 (positive) and 1,25D (negative) underline the relevant inhibitory action of Sclerostin on vitamin D activation. In conclusion, Sclerostin levels in KTR are normal and influenced more by bone turnover than by eGFR. Its involvement with other hormones of mineral homeostasis (FGF23/Klotho and Vitamin D) is part of the sophisticated cross-talk between bone and the kidney.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Interactions of sclerostin with FGF23, soluble klotho and vitamin D in renal transplantation

et al. 2017

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“…In bone tissue, because of the presence of high levels of collagens containing BMPs interaction specific site, these BMPs are sequestered in the ECM, and the solid induction mode is favored over the punctual induction mode. Diseases in different tissues are caused by malfunctions in the BMP signaling pathways (Ramirez and Rifkin, 2009; Maciel et al, 2010; Mazzaferro et al, 2010; Sethi and Kang, 2011). …”

Section: Introductionmentioning

confidence: 99%

Insights into the osteoblast precursor differentiation towards mature osteoblasts induced by continuous BMP-2 signaling

et al. 2013

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SummaryMature osteoblasts are the cells responsible for bone formation and are derived from precursor osteoblasts. However, the mechanisms that control this differentiation are poorly understood. In fact, unlike the majority of organs in the body, which are composed of “soft” tissue from which cells can easily be isolated and studied, the “hard” mineralized tissue of bone has made it difficult to study the function of bone cells. Here, we established an in vitro model that mimics this differentiation under physiological conditions. We obtained mature osteoblasts and characterized them on the basis of the following parameters: the strong expression of osteoblastic markers, such as Runx2 and Col-I; the achievement of specific dimensions (the cell volume increases 26-fold compared to the osteoblast precursors); and the production of an abundant extracellular matrix also called osteoid. We demonstrated that the differentiation of osteoblast precursors into mature osteoblasts requires the continuous activation of Bone Morphogenetic Protein (BMP) receptors, which we established with the immobilization of a BMP-2mimetic peptide on a synthetic matrix mimicking in vivo microenvironment. Importantly, we demonstrated that the organization of the F-actin network and acetylated microtubules of the cells were modified during the differentiation process. We showed that the perturbation of the F-actin cytoskeleton organization abolished the differentiation process. In addition, we demonstrated that expression of the Runx2 gene is required for this differentiation. These findings demonstrate the retro-regulation of cytoplasmic and genic components due to the continuous induction of BMP-2 and also provide more detailed insights into the correct signaling of BMPs for cell differentiation in bone tissue.

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“…For example, the originally described mode of action of FGF23 in mineral homeostasis allowed to evidentiate part of the complex link between bone and kidney [1] and to better classify some metabolic diseases [2]. However, it is becoming increasingly evident that in chronic renal failure in particular, FGF23 (alone or in combination with other bone proteins) also explains in part the link between CKD and cardiovascular disease [3].…”

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confidence: 99%

Bone in CKD: why the ERA EDTA CKD-MBD working group organized a dedicated meeting?

et al. 2017

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The bone and the kidney

Cited by 28 publications

References 116 publications

Interactions of sclerostin with FGF23, soluble klotho and vitamin D in renal transplantation

Interactions of sclerostin with FGF23, soluble klotho and vitamin D in renal transplantation

Insights into the osteoblast precursor differentiation towards mature osteoblasts induced by continuous BMP-2 signaling

Bone in CKD: why the ERA EDTA CKD-MBD working group organized a dedicated meeting?

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