Protective effect of epigenetic silencing of CyclinD1 against spinal cord injury using bone marrow-derived mesenchymal stem cells in rats

J Cell Physiol. 2018 Jul;233(7):5361-5369. doi: 10.1002/jcp.26354. Epub 2018 Jan 23.

Abstract

This study focuses on the protective effect of epigenetic silencing of CyclinD1 against spinal cord injury (SCI) using bone marrow-derived mesenchymal stem cells (BMSCs) in rats. Eighty-eight adult female Wistar rats were randomly assigned into the sham group, the control group, the si-CyclinD1 + BMSCs group and the BMSCs group. CyclinD1 protein and mRNA expressions after siRNA transfection were detected by Western blotting and qRT-PCR. The siRNA-CyclinD1 BMSCs were transplanted into rats in the si-CyclinD1 + BMSCs group using stereotaxic method 6 hr after SCI. Hindlimb locomotor performance was determined using inclined plane test and Basso-Beattie-Bresnahan (BBB) locomotor rating scale. Expressions of glial fibrillary acidic protein (GFAP) and nerve growth factor (NGF) were detected by immunohistochemistry. Inclined plane and BBB scores in the control, si-CyclinD1 + BMSCs, and BMSCs groups were significantly lower than the sham group, but these scores were evidently decreased in the control group and increased in the si-CyclinD1 + BMSCs group compared with the BMSCs group. The repair degree of spinal cord tissues of rats in the si-CyclinD1 + BMSCs group was obvious than the BMSCs group. GFAP and NGF protein expressions were markedly decreased in the control, si-CyclinD1 + BMSCs and BMSCs groups when compared with the sham group. GFAP- and NGF-positive cells were significantly increased in the si-CyclinD1 + BMSCs group while decreased in the control group. Our study provides evidence that epigenetic silencing of CyclinD1 using BMSCs might accelerate the repair of SCI in rats.

Keywords: CyclinD1 gene silencing; bone marrow; locomotor performance; mesenchymal stem cells; spinal cord injury.

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Cyclin D1 / antagonists & inhibitors
  • Cyclin D1 / genetics*
  • Disease Models, Animal
  • Epigenesis, Genetic / genetics*
  • Gene Expression Regulation, Developmental / genetics
  • Gene Silencing
  • Glial Fibrillary Acidic Protein
  • Humans
  • Locomotion / genetics
  • Locomotion / physiology
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology
  • RNA, Small Interfering / genetics
  • Rats
  • Receptor, Nerve Growth Factor / genetics
  • Recovery of Function / genetics
  • Spinal Cord / physiopathology
  • Spinal Cord Injuries / genetics*
  • Spinal Cord Injuries / physiopathology
  • Spinal Cord Injuries / therapy

Substances

  • Ccnd1 protein, rat
  • GFAP protein, rat
  • Glial Fibrillary Acidic Protein
  • RNA, Small Interfering
  • Receptor, Nerve Growth Factor
  • Cyclin D1