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Matrix extracellular phosphoglycoprotein is expressed in causative tumors of oncogenic osteomalacia

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Abstract

Oncogenic osteomalacia (OOM), or tumor-induced osteomalacia, is a rare disease characterized by renal phosphate wasting and osteomalacia. It arises due to the secretion of fibroblast growth factor 23 (FGF-23) from causative tumors. Matrix extracellular phosphoglycoprotein (MEPE) is predominantly expressed in odontoblasts, osteoblasts, and osteocytes. Although the presence of MEPE mRNA has been reported in some OOM tumors, little is known about the prevalence of MEPE expression in OOM tumors. In this study, the expression of MEPE and FGF-23 in OOM tumors was investigated at the transcriptional and translational levels. Eleven causative OOM tumors were analyzed by quantitative real-time reverse transcription-polymerase chain reaction and immunohistochemistry for MEPE and FGF-23 expression. Hemangiopericytomas and giant cell tumors, pathological diagnoses that are common in cases of OOM, were obtained from non-osteomalacic patients and analyzed as controls. The gene expression level of FGF23 and MEPE in OOM tumors was 104- and 105-times higher, respectively, than in non-OOM tumors. Immunohistochemical staining revealed that FGF-23 protein was expressed in all OOM tumors, and MEPE was expressed in 10 out of 11 OOM tumors. Thus, MEPE expression was common in OOM tumors, similar to FGF-23. These results indicate that, in addition to the hypophosphatemic effects of FGF-23, MEPE or the MEPE-derived acidic serine aspartate-rich MEPE-associated motif peptide may contribute to decreased bone mineralization in OOM patients.

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Acknowledgments

We greatly thank Dr. Jeffrey Lavigne (Immutopics, Inc.) for providing the goat anti-hFGF-23 antibody. This work was supported by two Grant-in-Aids for Scientific Research (C) (20591101 to Y.I. and 20590980 to M.I. and Y.I.), a grant from The Kidney Foundation, Japan (JKFB09-7 to Y.I.), and the JOS Distinguished Paper Award from the Japan Osteoporosis Society.

Conflict of interest

None to declare.

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Authors and Affiliations

  1. Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan

    Yasuo Imanishi, Keisuke Kobayashi, Yuki Nagata, Tomoaki Morioka, Katsuhito Mori & Masaaki Inaba

  2. Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Japan

    Jun Hashimoto & Wataru Ando

  3. Department of Orthopaedic Surgery, Osaka National Hospital, Osaka, Japan

    Takafumi Ueda

  4. Miyauchi Medical Center, Takatuski, Japan

    Akimitsu Miyauchi

  5. Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Hajime M. Koyano

  6. Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

    Hiroshi Kaji

  7. Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan

    Takatoshi Saito

  8. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Koichi Oba

  9. Department of Endocrinology, Kyoto City Hospital, Kyoto, Japan

    Yasato Komatsu

  10. Department of Geriatrics and Neurology, Osaka City University Graduate School of Medicine, Osaka, Japan

    Takami Miki

Authors
  1. Yasuo Imanishi
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  2. Jun Hashimoto
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  3. Wataru Ando
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  4. Keisuke Kobayashi
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  5. Takafumi Ueda
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  6. Yuki Nagata
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  7. Akimitsu Miyauchi
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  8. Hajime M. Koyano
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  9. Hiroshi Kaji
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  10. Takatoshi Saito
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  11. Koichi Oba
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  12. Yasato Komatsu
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  13. Tomoaki Morioka
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  14. Katsuhito Mori
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  15. Takami Miki
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  16. Masaaki Inaba
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Corresponding author

Correspondence to Yasuo Imanishi.

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Imanishi, Y., Hashimoto, J., Ando, W. et al. Matrix extracellular phosphoglycoprotein is expressed in causative tumors of oncogenic osteomalacia. J Bone Miner Metab 30, 93–99 (2012). https://doi.org/10.1007/s00774-011-0290-8

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  • DOI: https://doi.org/10.1007/s00774-011-0290-8

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