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SDF1/CXCR7 Signaling Axis Participates in Angiogenesis in Degenerated Discs via the PI3K/AKT Pathway

Hanxiang Zhang1, Peng Wang1, Xiang Zhang1

  • 1Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.

DNA and Cell Biology
|March 14, 2019
PubMed

Insights

Degenerative disc disease involves blood vessel growth. The SDF1/CXCR7 pathway promotes this angiogenesis in degenerated discs via PI3K/AKT signaling.

Area of Science:

  • Biomedical Engineering
  • Cell Biology
  • Orthopedics

Background:

  • Degenerative disc disease (DDD) is a primary cause of low back pain.
  • Neovascularization (angiogenesis) is a key pathological feature of DDD in intervertebral discs (IVDs).
  • The stromal cell-derived factor 1 (SDF1)/CXCR7 signaling axis is implicated in physiological and pathological vascularization processes.

Purpose of the Study:

  • To investigate the role of the SDF1/CXCR7 signaling axis in the angiogenesis of degenerated IVDs.
  • To elucidate the underlying molecular mechanisms by which this axis influences IVD angiogenesis.
  • To determine the involvement of downstream signaling pathways in SDF1/CXCR7-mediated angiogenesis.

Main Methods:

  • Coculture of human nucleus pulposus cells (NPCs) and vascular endothelial cells (VECs).
  • Manipulation of SDF1 and CXCR7 expression levels to assess effects on VEC angiogenesis.
  • Analysis of downstream signaling pathways, specifically the PI3K/AKT pathway, including assessment of pAKT and PTEN levels.

Main Results:

  • Increased SDF1 expression enhanced VEC angiogenesis in the coculture system.
  • Inhibition of CXCR7 significantly reduced VEC angiogenesis.
  • The PI3K/AKT pathway was identified as a downstream mediator; increased pAKT or decreased PTEN levels correlated with enhanced VEC angiogenesis induced by NPCs.

Conclusions:

  • The SDF1/CXCR7 signaling axis is a significant contributor to angiogenesis in degenerated intervertebral discs.
  • This process is mediated through the activation of the PI3K/AKT signaling pathway.
  • Targeting the SDF1/CXCR7/PI3K/AKT axis may offer therapeutic strategies for managing DDD-related neovascularization.

Keywords:
CXCR7PI3K/AKTangiogenesisdegenerated discstromal cell-derived factor 1 (SDF1)

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