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

J Bone Miner Metab. 2019 May;37(3):467-474. doi: 10.1007/s00774-018-0954-8. Epub 2018 Sep 5.

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.

Keywords: Fibroblast growth factor 2; GABRB1; Human dental pulp cells; Spinal cord injury.

MeSH terms

  • Animals
  • Dental Pulp / cytology*
  • Disease Models, Animal
  • Electrophysiological Phenomena / drug effects
  • Fibroblast Growth Factor 2 / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Humans
  • Motor Activity / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Spinal Cord Injuries / genetics*
  • Spinal Cord Injuries / physiopathology
  • Spinal Cord Injuries / therapy*

Substances

  • Fibroblast Growth Factor 2