ECTS Abstracts (2015) 1 P405

Elevated Osterix Expression Enhanced FGF-23 Secretion from Causative Tumours of Oncogenic Osteomalacia

Masaya Ohara, Yasuo Imanishi, Yuki Nagata, Tomomi Maeda, Ikue Kobayashi, Katsuhito Mori & Masaaki Inaba

Department of Metabolism, Endocrinology & Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.

Background: Oncogenic osteomalacia (OOM), or tumour induced osteomalacia (TIO), is a rare disease characterised by renal phosphate wasting and hypophosphataemic osteomalacia due to the secretion of fibroblast growth factor 23 (FGF-23) from causative mesenchymal OOM tumours, which is physiologically secreted from osteocytes. To determine whether OOM tumours have osteogenic characteristics, the expressions of osteoblast/osteocyte specific genes in OOM tumours were investigated at the transcriptional and translational levels.

Methods: Sixteen causative OOM tumours and 7 histopathologic classification-matched non-OOM tumours were analysed by quantitative real-time RT-PCR and immunohistochemistry. Fluorescent immunohistochemistry was also applied to investigate co-localisation of the gene expressions in OOM tumours. The study was approved by the institutional ethics committees and was conducted in accordance with the principles of the Declaration of Helsinki. UMR106 osteoblastic cell line was analysed to identify the role of osteocyte/osteoblast specific genes in FGF-23 expression in vitro.

Results: Osteocyte/osteoblast specific genes such as osterix (OSX), osteocalcin (BGP), and DMP-1 were significantly elevated as well as FGF-23 in OOM tumours compared with non-OOM tumours. The elevated expressions of these genes were also confirmed by immunhistochemistry. Fluorescent immunohistochemistry revealed that localisations of these gene expressions were merged in some OOM tumours, however, the other OOM tumours exhibited different co-localisations of OSX and FGF-23, from those of osteocalcin and DMP-1. Gene knockdown analyses using siRNA of each genes in UMR106 cells revealed that FGF-23 expression was elevated by OSX, but decreased by DMP-1. BGP decreased DMP-1 expression, but OSX had no effect on BGP or DMP-1 expressions.

Conclusion: OOM tumours have osteogenic characteristics. Different co-localisation of osteocyte/osteoblast specific genes and independent signal pathways of OSX to FGF-23 from BGP to DMP-1 suggests overexpression of OSX is one of a cause of FGF-23 secretion from OOM tumours.

Disclosure: The authors declared no competing interests.

Article tools

My recent searches

No recent searches.