Skip to main content
Top
Published in: Journal of Bone and Mineral Metabolism 3/2019

01-05-2019 | Original Article

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

Authors: 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 Tezuka

Published in: Journal of Bone and Mineral Metabolism | Issue 3/2019

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Le Blank K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringden O (2008) Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371:1579–1586CrossRef Le Blank K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringden O (2008) Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371:1579–1586CrossRef
2.
go back to reference Tannna T, Sachan V (2014) Mesenchymal stem cells: potential in treatment of neurodegenerative diseases. Curr Stem Cell Res Ther 9:513–521CrossRef Tannna T, Sachan V (2014) Mesenchymal stem cells: potential in treatment of neurodegenerative diseases. Curr Stem Cell Res Ther 9:513–521CrossRef
4.
go back to reference Chai Y, Jiang X, Ito Y, Bringas P Jr, Han J, Rowitch DH, Soriano P, McMahon AP, Sucov HM (2000) Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis. Development 127:1671–1679PubMed Chai Y, Jiang X, Ito Y, Bringas P Jr, Han J, Rowitch DH, Soriano P, McMahon AP, Sucov HM (2000) Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis. Development 127:1671–1679PubMed
5.
go back to reference Gronthos S, Brahim J, Li W, Fisher LW, Cherman N, Boyde A, DenBesten P, Robey PG, Shi S (2002) Stem cell properties of human dental pulp stem cells. J Dent Res 81:531–535CrossRefPubMed Gronthos S, Brahim J, Li W, Fisher LW, Cherman N, Boyde A, DenBesten P, Robey PG, Shi S (2002) Stem cell properties of human dental pulp stem cells. J Dent Res 81:531–535CrossRefPubMed
6.
go back to reference Yamazaki H, Tsuneto M, Yoshino M, Ymamura K, Hayashi S (2007) Potential of dental mesenchymal cells in developing teeth. Stem Cells 25:78–87CrossRefPubMed Yamazaki H, Tsuneto M, Yoshino M, Ymamura K, Hayashi S (2007) Potential of dental mesenchymal cells in developing teeth. Stem Cells 25:78–87CrossRefPubMed
7.
go back to reference Takeda T, Tezuka Y, Horiuchi M, Hosono K, Iida K, Hatakeyama D, Miyaki S, Kunisada T, Shibata T, Tezuka K (2008) Characterization of dental pulp stem cells of human tooth germs. J Dent Res 87:676–681CrossRefPubMed Takeda T, Tezuka Y, Horiuchi M, Hosono K, Iida K, Hatakeyama D, Miyaki S, Kunisada T, Shibata T, Tezuka K (2008) Characterization of dental pulp stem cells of human tooth germs. J Dent Res 87:676–681CrossRefPubMed
8.
go back to reference Iida K, Takeda-Kawaguchi T, Tezuka Y, Kunisada T, Shibata T, Tezuka K (2010) Hypoxia enhances colony formation and proliferation but inhibits differentiation of human dental pulp stem cells. Arch Oral Biol 55:648–654CrossRefPubMed Iida K, Takeda-Kawaguchi T, Tezuka Y, Kunisada T, Shibata T, Tezuka K (2010) Hypoxia enhances colony formation and proliferation but inhibits differentiation of human dental pulp stem cells. Arch Oral Biol 55:648–654CrossRefPubMed
9.
go back to reference Iida K, Takeda-Kawaguchi T, Hada M, Yuriguchi M, Aoki H, Tamaoki N, Hatakeyama D, Kunisada T, Shibata T, Tezuka K (2013) Hypoxia-enhanced derivation of iPSCs from human dental pulp cells. J Dent Res 92:905–910CrossRefPubMed Iida K, Takeda-Kawaguchi T, Hada M, Yuriguchi M, Aoki H, Tamaoki N, Hatakeyama D, Kunisada T, Shibata T, Tezuka K (2013) Hypoxia-enhanced derivation of iPSCs from human dental pulp cells. J Dent Res 92:905–910CrossRefPubMed
10.
go back to reference Takeda-Kawaguchi T, Sugiyama K, Chikusa S, Iida K, Aoki H, Tamaoki N, Hatakeyama D, Kunisada T, Shibata T, Fusaki N, Tezuka K (2014) Derivation of iPSCs after culture of human dental pulp cells under defined conditions. PLoS One 9:e115392CrossRefPubMedPubMedCentral Takeda-Kawaguchi T, Sugiyama K, Chikusa S, Iida K, Aoki H, Tamaoki N, Hatakeyama D, Kunisada T, Shibata T, Fusaki N, Tezuka K (2014) Derivation of iPSCs after culture of human dental pulp cells under defined conditions. PLoS One 9:e115392CrossRefPubMedPubMedCentral
11.
go back to reference Tamaoki N, Takahashi K, Tanaka T, Ichisaka T, Aoki H, Takeda-Kawaguchi T, Iida K, Hatakeyama D, Kunisada T, Shibata T, Tezuka K (2010) Dental pulp cells for induced pluripotent stem cell banking. J Dent Res 89:773–778CrossRefPubMed Tamaoki N, Takahashi K, Tanaka T, Ichisaka T, Aoki H, Takeda-Kawaguchi T, Iida K, Hatakeyama D, Kunisada T, Shibata T, Tezuka K (2010) Dental pulp cells for induced pluripotent stem cell banking. J Dent Res 89:773–778CrossRefPubMed
12.
go back to reference Okita K, Matsumura Y, Sato Y, Okada A, Morizane A, Okamoto S, Hong H, Nakagawa M, Tanabe K, Tezuka K, Shibata T, Kunisada T, Takahashi M, Takahashi J, Saji H, Yamanaka S (2011) A more efficient method to generate integration-free human iPS cells. Nat Method 8:409–412CrossRef Okita K, Matsumura Y, Sato Y, Okada A, Morizane A, Okamoto S, Hong H, Nakagawa M, Tanabe K, Tezuka K, Shibata T, Kunisada T, Takahashi M, Takahashi J, Saji H, Yamanaka S (2011) A more efficient method to generate integration-free human iPS cells. Nat Method 8:409–412CrossRef
13.
go back to reference Tamaoki N, Takahashi K, Aoki H, Iida K, Kawaguchi T, Hatakeyama D, Inden M, Chosa N, Ishisaki A, Kunisada T, Shibata T, Goshima N, Yamanaka S, Tezuka K (2014) The homeobox gene DLX4 promotes generation of human induced pluripotent stem cells. Sci Rep 4:7283CrossRefPubMedPubMedCentral Tamaoki N, Takahashi K, Aoki H, Iida K, Kawaguchi T, Hatakeyama D, Inden M, Chosa N, Ishisaki A, Kunisada T, Shibata T, Goshima N, Yamanaka S, Tezuka K (2014) The homeobox gene DLX4 promotes generation of human induced pluripotent stem cells. Sci Rep 4:7283CrossRefPubMedPubMedCentral
14.
go back to reference Harrop JS, Hashimoto R, Norvell D, Raich A, Aarabi B, Grossman RG, Guest JD, Tator CH, Chapman J, Fehlings MG (2012) Evaluation of clinical experience using cell-based therapies in patients with spinal cord injury: a systematic review. J Neurosurg Spine 17:230–246CrossRefPubMed Harrop JS, Hashimoto R, Norvell D, Raich A, Aarabi B, Grossman RG, Guest JD, Tator CH, Chapman J, Fehlings MG (2012) Evaluation of clinical experience using cell-based therapies in patients with spinal cord injury: a systematic review. J Neurosurg Spine 17:230–246CrossRefPubMed
15.
go back to reference Sakai K, Yamamoto A, Matsubara K, Nakamura S, Naruse M, Yamagata M, Sakamoto K, Tauchi R, Wakao N, Imagama S, Hibi H, Kadomatsu K, Ishiguro N, Ueda M (2012) Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms. J Clin Investig 122:80–90PubMed Sakai K, Yamamoto A, Matsubara K, Nakamura S, Naruse M, Yamagata M, Sakamoto K, Tauchi R, Wakao N, Imagama S, Hibi H, Kadomatsu K, Ishiguro N, Ueda M (2012) Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms. J Clin Investig 122:80–90PubMed
16.
go back to reference Matsubara K, Matsushita Y, Sakai K, Kano F, Kondo M, Noda M, Hashimoto N, Imagama S, Ishiguro N, Suzumura A, Ueda M, Furukawa K, Yamamoto A (2015) Secreted ectodomain of sialic acid-binding Ig-like lectin-9 and monocyte chemoattractant protein-1 promote recovery after rat spinal cord injury by altering macrophage polarity. J Neurosci 35:2452–2464CrossRefPubMedPubMedCentral Matsubara K, Matsushita Y, Sakai K, Kano F, Kondo M, Noda M, Hashimoto N, Imagama S, Ishiguro N, Suzumura A, Ueda M, Furukawa K, Yamamoto A (2015) Secreted ectodomain of sialic acid-binding Ig-like lectin-9 and monocyte chemoattractant protein-1 promote recovery after rat spinal cord injury by altering macrophage polarity. J Neurosci 35:2452–2464CrossRefPubMedPubMedCentral
17.
go back to reference Nagashima K, Miwa T, Soumiya H, Ushiro D, Takeda-Kawaguchi T, Tamaoki N, Ishiguro S, Sato Y, Miyamoto K, Ohno T, Osawa M, Kunisada T, Shibata T, Tezuka K, Furukawa S, Fukumitsu H (2017) Priming with FGF2 stimulates human dental pulp cells to promote axonal regeneration and locomotor function recovery after spinal cord injury. Sci Rep 7:13500CrossRefPubMedPubMedCentral Nagashima K, Miwa T, Soumiya H, Ushiro D, Takeda-Kawaguchi T, Tamaoki N, Ishiguro S, Sato Y, Miyamoto K, Ohno T, Osawa M, Kunisada T, Shibata T, Tezuka K, Furukawa S, Fukumitsu H (2017) Priming with FGF2 stimulates human dental pulp cells to promote axonal regeneration and locomotor function recovery after spinal cord injury. Sci Rep 7:13500CrossRefPubMedPubMedCentral
18.
go back to reference Kasai M, Jikoh T, Fukumitsu H, Furukawa S (2014) FGF-2 responsive and spinal cord-resident cells improve locomotor function after spinal cord injury. J Neurotrauma 31:1584–1598CrossRefPubMedPubMedCentral Kasai M, Jikoh T, Fukumitsu H, Furukawa S (2014) FGF-2 responsive and spinal cord-resident cells improve locomotor function after spinal cord injury. J Neurotrauma 31:1584–1598CrossRefPubMedPubMedCentral
19.
go back to reference Lu P, Wang Y, Graham L, McHale K, Gao M, Wu D, Brock J, Blesch A, Rosenzweig ES, Havton LA, Zheng B, Conner JM, Marsala M, Tuszynski MH (2012) Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Cell 150:1264–1273CrossRefPubMedPubMedCentral Lu P, Wang Y, Graham L, McHale K, Gao M, Wu D, Brock J, Blesch A, Rosenzweig ES, Havton LA, Zheng B, Conner JM, Marsala M, Tuszynski MH (2012) Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Cell 150:1264–1273CrossRefPubMedPubMedCentral
20.
go back to reference Kunisada T, Tezuka K, Aoki H, Motohashi T (2014) The stemness of neural crest cells and their derivatives. Birth Defects Res C Embryo Today 102:251–262CrossRef Kunisada T, Tezuka K, Aoki H, Motohashi T (2014) The stemness of neural crest cells and their derivatives. Birth Defects Res C Embryo Today 102:251–262CrossRef
21.
go back to reference Wu LW, Wang YL, Christensen JM, Khalifian S, Schneeberger S, Raimondi G, Cooney DS, Lee WP, Brandacher G (2014) Donor age negatively affects the immunoregulatory properties of both adipose and bone marrow derived mesenchymal stem cells. Transpl Immunol 30:122–127CrossRefPubMed Wu LW, Wang YL, Christensen JM, Khalifian S, Schneeberger S, Raimondi G, Cooney DS, Lee WP, Brandacher G (2014) Donor age negatively affects the immunoregulatory properties of both adipose and bone marrow derived mesenchymal stem cells. Transpl Immunol 30:122–127CrossRefPubMed
22.
go back to reference Nakatsuji N, Nakajima F, Tokunaga K (2008) HLA-haplotype banking and iPS cells. Nat Biotechnol 26:739–740CrossRef Nakatsuji N, Nakajima F, Tokunaga K (2008) HLA-haplotype banking and iPS cells. Nat Biotechnol 26:739–740CrossRef
23.
go back to reference Xu W, Chi L, Xu R, Ke Y, Luo C, Cai J, Qiu M, Gozal D, Liu R (2005) Increased production of reactive oxygen species contributes to motor neuron death in a compression mouse model of spinal cord injury. Spinal Cord 43:204–213CrossRefPubMed Xu W, Chi L, Xu R, Ke Y, Luo C, Cai J, Qiu M, Gozal D, Liu R (2005) Increased production of reactive oxygen species contributes to motor neuron death in a compression mouse model of spinal cord injury. Spinal Cord 43:204–213CrossRefPubMed
24.
go back to reference Ohashi M, Hirano T, Watanabe K, Shoji H, Ohashi N, Baba H, Endo N, Kohno T (2016) Hydrogen peroxide modulates neuronal excitability and membrane properties in ventral horn neurons of the rat spinal cord. Neuroscience 331:206–220CrossRefPubMed Ohashi M, Hirano T, Watanabe K, Shoji H, Ohashi N, Baba H, Endo N, Kohno T (2016) Hydrogen peroxide modulates neuronal excitability and membrane properties in ventral horn neurons of the rat spinal cord. Neuroscience 331:206–220CrossRefPubMed
25.
go back to reference Parker DA, Marino V (2013) GABA heteroreceptors modulate noradrenaline release in human dental pulp. J Dent Res 92:1017–1021CrossRefPubMed Parker DA, Marino V (2013) GABA heteroreceptors modulate noradrenaline release in human dental pulp. J Dent Res 92:1017–1021CrossRefPubMed
Metadata
Title
FGF2-responsive genes in human dental pulp cells assessed using a rat spinal cord injury model
Authors
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 Tezuka
Publication date
01-05-2019
Publisher
Springer Japan
Published in
Journal of Bone and Mineral Metabolism / Issue 3/2019
Print ISSN: 0914-8779
Electronic ISSN: 1435-5604
DOI
https://doi.org/10.1007/s00774-018-0954-8

Other articles of this Issue 3/2019

Journal of Bone and Mineral Metabolism 3/2019 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.