Total for the last 12 months
number of access : ?
number of downloads : ?
ID 113624
Author
Kinoshita, Yuka The University of Tokyo
Takashi, Yuichi Tokushima University
Ito, Nobuaki The University of Tokyo
Ikegawa, Shiro RIKEN Center for Integrative Medical Sciences
Mano, Hiroyuki National Cancer Center Research Institute
Ushiku, Tetsuo The University of Tokyo
Fukayama, Masashi The University of Tokyo
Nangaku, Masaomi The University of Tokyo
Keywords
Tumor-induced osteomalacia (TIO)
Klotho
Fibroblast growth factor 23 (FGF23)
FGF receptor (FGFR)
Hypophosphatemia
Content Type
Journal Article
Description
Tumor-induced rickets/osteomalacia (TIO) is a rare paraneoplastic syndrome caused by tumors that ectopically express fibroblast growth factor 23 (FGF23). FGF23 is a bone-derived hormone that regulates serum phosphate concentrations. Patients with TIO develop hypophosphatemic rickets/osteomalacia due to FGF23 excess and suffer from symptoms such as leg deformities, bone pain, skeletal muscle myopathy, and multiple fractures/ pseudofractures. Usually, successful surgical removal of the causative tumors normalizes serum FGF23 and phosphate concentrations in patients with TIO. Most FGF23-producing tumors associated with TIO are histologically called phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT). The precise mechanism by which these tumors ectopically overproduce FGF23 outside of bone is yet to be clarified. Therefore, we performed an RNA sequencing analysis of a PMTMCT that was found in the left parotid gland of a patient with TIO. Among the upregulated genes, we focused on Klotho, the protein product of which is a single pass transmembrane protein that works along with an FGF receptor 1c as a receptor complex for FGF23. Subsequent histological analysis confirmed the ectopic expression of Klotho in other PMTMCTs. From these results, we assume that the ectopic expression of Klotho in PTMMCTs enables a positive feedback loop in FGF23 production via the activation of FGF receptor 1c and exacerbates disease manifestations in TIO.
Journal Title
Bone Reports
ISSN
23521872
Publisher
Elsevier
Volume
10
Start Page
100192
Published Date
2018-12-31
Rights
© 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences