Journal of Bone and Mineral Metabolism

, Volume 37, Issue 3, pp 467–474 | Cite as

FGF2-responsive genes in human dental pulp cells assessed using a rat spinal cord injury model

  • Ken Sugiyama
  • Kosuke Nagashima
  • Takahiro Miwa
  • Yuta Shimizu
  • Tomoko Kawaguchi
  • Kazuki Iida
  • Naritaka Tamaoki
  • Daijiro Hatakeyama
  • Hitomi Aoki
  • Chikara Abe
  • Hironobu Morita
  • Takahiro Kunisada
  • Toshiyuki Shibata
  • Hidefumi Fukumitsu
  • Ken-ichi TezukaEmail author
Original Article


The central nervous system in adult mammals does not heal spontaneously after spinal cord injury (SCI). However, SCI treatment has been improved recently following the development of cell transplantation therapy. We recently reported that fibroblast growth factor (FGF) 2-pretreated human dental pulp cells (hDPCs) can improve recovery in a rat model of SCI. This study aimed to investigate mechanisms underlying the curative effect of SCI enhanced via FGF2 pretreatment; we selected three hDPC lines upon screening for the presence of mesenchymal stem cell markers and of their functionality in a rat model of SCI, as assessed using the Basso, Beattie, and Bresnahan score of locomotor functional scale, electrophysiological tests, and morphological analyses. We identified FGF2-responsive genes via gene expression analyses in these lines. FGF2 treatment upregulated GABRB1, MMP1, and DRD2, which suggested to contribute to SCI or central the nervous system. In an expanded screening of additional lines, GABRB1 displayed rather unique and interesting behavior; two lines with the lowest sensitivity of GABRB1 to FGF2 treatment displayed an extremely minor effect in the SCI model. These findings provide insights into the role of FGF2-responsive genes, especially GABRB1, in recovery from SCI, using hDPCs treated with FGF2.


Human dental pulp cells Spinal cord injury Fibroblast growth factor 2 GABRB1 



We wish to thank Editage ( for English language editing. This study was supported by the Japan Society for the Promotion of Science (KAKENHI Grant Numbers JP23592697, JP26670799, JP26463001, JP26293426, JP26463000 and JP17H06731).

Additional information

Accession codes: the microarray data were submitted to the NCBI GEO database under the accession number (GSE83902).

Compliance with ethical standards

Ethical approval

All procedures involving human participants were performed in accordance with the ethical standards of the institutional and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All applicable institutional and national guidelines for the care and use of animals were followed.

Conflict of interest

This manuscript was partly developed with support from Daiichi Sankyo Company Ltd.

Supplementary material

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Copyright information

© The Japanese Society for Bone and Mineral Research and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  • Ken Sugiyama
    • 1
  • Kosuke Nagashima
    • 2
  • Takahiro Miwa
    • 2
  • Yuta Shimizu
    • 3
  • Tomoko Kawaguchi
    • 1
  • Kazuki Iida
    • 1
  • Naritaka Tamaoki
    • 1
  • Daijiro Hatakeyama
    • 1
  • Hitomi Aoki
    • 4
  • Chikara Abe
    • 5
  • Hironobu Morita
    • 5
  • Takahiro Kunisada
    • 4
  • Toshiyuki Shibata
    • 1
  • Hidefumi Fukumitsu
    • 2
  • Ken-ichi Tezuka
    • 4
    • 6
    Email author
  1. 1.Department of Oral and Maxillofacial ScienceGifu University Graduate School of MedicineGifuJapan
  2. 2.Laboratory of Molecular BiologyGifu Pharmaceutical UniversityGifuJapan
  3. 3.Department of PeriodontologyAsahi University School of DentistryMizuhoJapan
  4. 4.Department of Tissue and Organ DevelopmentGifu University Graduate School of MedicineGifuJapan
  5. 5.Department of PhysiologyGifu University Graduate School of MedicineGifuJapan
  6. 6.Center for Highly Advanced Integration of Nano and Life SciencesGifu University (G-CHAIN)GifuJapan

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