T140 Inhibits Apoptosis and Promotes Proliferation and Matrix Formation Through the SDF-1/CXC Receptor-4 Signaling Pathway in Endplate Chondrocytes of the Rat Intervertebral Discs

World Neurosurg. 2020 Jan:133:e165-e172. doi: 10.1016/j.wneu.2019.08.140. Epub 2019 Aug 30.

Abstract

Background: Cartilaginous endplate (CEP), a thin layer of hyaline cartilage located between the vertebral endplate and nucleus pulposus, transports the nutrient into the disc. The objective of this study was to evaluate the influence of T140 (polyphemusin II-derived peptide) on the CEP cell growth, apoptosis, and the matrix formation via the stromal cell-derived factor-1 (SDF-1)/cysteine X cysteine (CXC) receptor-4 (CXCR4) signaling pathway.

Methods: Sprague-Dawley rats were euthanized by cervical dislocation and dissected for the isolation and the appraisal of CEP cells that were extracted from the endplate in rat intervertebral discs and were then added with different concentrations of reagents (SDF-1 and T140). The effect of T140 on CEP cell proliferation and apoptosis were analyzed. The messenger RNA (mRNA) and protein expressions of CXCR4, prominin-1, proteoglycans, type II collagen, B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein were analyzed by reverse transcription quantitative polymerase chain reaction and Western blot analysis.

Results: T140 promoted the proliferation of CEP cells and inhibited the apoptosis of CEP cells. Additionally, T140 suppressed the mRNA and protein expression of CXCR4, prominin-1, and Bcl-2 associated X protein, and increased the mRNA and protein expression of proteoglycans, type II collagen, and Bcl-2.

Conclusions: T140 promotes the proliferation and matrix formation and inhibits the apoptosis of CEP cells by blocking the SDF-1/CXCR4 signaling pathway in vitro, which provides a certain therapeutic effect on the degeneration of intervertebral discs.

Keywords: Apoptosis; Cartilage endplate cells; Matrix formation; Polyphemusin II-derived peptide; Proliferation; SDF-1/CXCR4 signaling pathway.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cell Division / drug effects
  • Chemokine CXCL12 / physiology*
  • Chondrocytes / drug effects*
  • Extracellular Matrix / drug effects*
  • Extracellular Matrix Proteins / drug effects
  • Gene Expression Regulation / drug effects
  • Hyaline Cartilage / cytology*
  • Intervertebral Disc / cytology*
  • Intervertebral Disc / drug effects
  • Male
  • Oligopeptides / pharmacology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, CXCR4 / physiology*
  • Signal Transduction / drug effects*

Substances

  • CXCL12 protein, rat
  • Chemokine CXCL12
  • Cxcr4 protein, rat
  • Extracellular Matrix Proteins
  • Oligopeptides
  • RNA, Messenger
  • Receptors, CXCR4
  • T140 peptide