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FGF23 - Fakten
Knochen ist HORMONELL aktiv !
Wirkung von FGF23:
• induziert Phosphaturie
• hemmt die renale 1,25D Produktion
Stimuli der FGF 23 Produktion:
• Vermehrte Phosphatzufuhr
• 1,25D
- ohne Vit. D
- Quartile aus 10.000 Pat.
- daraus ausgewählt:
n=200 Pat. starben in 1 Jahr
n=200 Kontrollen überlebten 1 Jahr
overallPO4
- 3,7-4,5 mg/dl
HR=0,72
p=0,03
- Früher Beginn einer Phosphatbindertherapie
- Phosphatbinder n= 3555
- Kein Phosphatbinder n=5055
RBK- Forschungs-Projekt Gewebedatenbank Nebenschilddrüse:
Expressionsmuster zahlreicher neuerer Faktoren (FGF-R, Klotho,
Vit.D-R, Ca-S-R, PTH, 1-alpha-Hydroxylase, …)
und
Korrelationen
mit klinischen Parametern
ASN 2009 Abstract F-PO1871]: Looping the Bone-Parathyroid
Axis: PTH Increases FGF23 Expression
Vardit Lavi-Moshayoff, Gilad Wasserman, Tally Naveh-Many, Justin Silver Nephrology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
Fibroblast growth factor 23 (FGF23) acts on the parathyroid to decrease PTH expression. We now report that PTH increases FGF23 expression. Adenine high Pi induced CKD rats at four days, had a marked increase in both serum PTH and FGF23 with no changes in serum calcium, Pi and 1,25(OH)2D (1,25D) suggesting a direct relationship between PTH and FGF23. Parathyroidectomy (PTX) corrected the high serum FGF23 levels. Remarkably, PTX completely prevented the rise in FGF23 in rats subsequently fed the adenine high Pi diet. Therefore, PTX both corrects and prevents the increased FGF23 of CKD. Minipump infusion of PTH increased serum FGF23, calvaria FGF23 mRNA and serum calcium levels in normal mice. To understand the mechanism of the direct effect of PTH on FGF23 we studied the expression of the upstream negative regulators of FGF23 in vivo and in vitro. CKD led to increased calvaria FGF23 mRNA levels and decreased Phex and DMP1 mRNA levels. In osteoblast-like UMR106 cells, PTH increased FGF23 mRNA levels and markedly decreased DMP1 (dentine matrix protein1), Phex(phosphate regulating hormone with homology to endopeptidase on the X chromosome) and MEPE (matrix extracellular phosphoglycoprotein) mRNA levels up to 48 h. DMP1 and MEPE increase Phex expression which leads to FGF23 protein degradation. The decrease in DMP1, MEPE and Phex by PTH would increase FGF23 protein levels. Our results show that in addition, PTH increases FGF23 gene expression. The effect of PTH on FGF23 mRNA may be either direct or mediated by Phex, DMP1 and/or MEPE. Therefore, PTH increases FGF23 expression in vivo and in vitro which together with the effect of FGF23 to decrease PTH completes a novel bone-parathyroid endocrine loop.