FGF23-FGF Receptor/Klotho Pathway as a New Drug Target for Disorders of Bone and Mineral Metabolism

被引：0
作者：
Seiji Fukumoto
机构：
[1] Tokushima University,Department of Nuclear Receptor Ligands and Vitamins Research, Fujii Memorial Institute of Medical Sciences
来源：
Calcified Tissue International | 2016年 / 98卷
关键词：
Rickets; Osteomalacia; Antibody; Klotho;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone produced by bone and works by binding to Klotho–FGF receptor complex. Excessive and deficient actions of FGF23 result in hypophosphatemic and hyperphosphatemic diseases, respectively. Therefore, it is reasonable to think that modulating FGF23 activities may be a novel therapeutic measure for these diseases. Several preclinical reports indicate that the inhibition of FGF23 activities ameliorates hypophosphatemic rickets/osteomalacia caused by excessive actions of FGF23. In addition, phase I–II clinical trials of anti-FGF23 antibody in adult patients with X-linked hypophosphatemia rickets, the most prevalent cause of genetic FGF23-related hypophosphatemic rickets, indicated that the antibody enhances renal tubular phosphate reabsorption and increases serum phosphate. However, it is not known whether the inhibition of FGF23 activities actually brings clinical improvement of rickets and osteomalacia. Available data indicate that FGF23-FGF receptor/Klotho pathway can be a new drug target for disorders of phosphate and bone metabolism.
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页码：334 / 340
页数：6
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[1]  
Fukumoto S(2009)Bone as an endocrine organ Trends Endocrinol Metab 20 230-236
[2]  
Martin TJ(2010)Direct evidence for a causative role of FGF23 in the abnormal renal phosphate handling and vitamin D metabolism in rats with early-stage chronic kidney disease Kidney Int 78 975-980
[3]  
Hasegawa H(2011)Anti-FGF23 neutralizing antibodies ameliorate muscle weakness and decreased spontaneous movement of Hyp mice J Bone Miner Res 26 803-810
[4]  
Nagano N(2009)Therapeutic effects of anti-FGF23 antibodies in hypophosphatemic rickets/osteomalacia J Bone Miner Res 24 1879-1888
[5]  
Urakawa I(2010)Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23-FGFR-Klotho complex formation Proc Natl Acad Sci USA 107 407-412
[6]  
Yamazaki Y(2011)Fibroblast growth factor 23 regulates renal 1,25-dihydroxyvitamin D and phosphate metabolism via the MAP kinase signaling pathway in Hyp mice J Bone Miner Res 26 1883-1890
[7]  
Iijima K(2011)FGF receptors control vitamin D and phosphate homeostasis by mediating renal FGF-23 signaling and regulating FGF-23 expression in bone J Bone Miner Res 26 2486-2497
[8]  
Fujita T(2013)Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets J Bone Miner Res 28 899-911
[9]  
Yamashita T(2012)Chronic inhibition of ERK1/2 signaling improves disordered bone and mineral metabolism in hypophosphatemic (Hyp) mice Endocrinology 153 1806-1816
[10]  
Fukumoto S(2014)Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia J Clin Invest 124 1587-1597
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