Mechanical loading of intervertebral disc modulates microglia proliferation, activation, and chemotaxis

S E Navone1, M Peroglio2, L Guarnaccia1

  • 1Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.

Abstract

Insights

Degenerating intervertebral discs (IVDs) create a neuroinflammatory environment that activates microglia. This activation exacerbates disc degeneration and may contribute to low back pain.

Area of Science:

  • Neuroscience
  • Immunology
  • Biomedical Engineering

Background:

  • Degenerative disc disease (DDD) is a significant cause of low back pain.
  • The role of neuroinflammation in DDD pathogenesis is increasingly recognized.
  • Microglia, the resident immune cells of the central nervous system, are implicated in inflammatory processes.

Purpose of the Study:

  • To investigate the impact of a mechanically induced degenerating intervertebral disc (IVD) microenvironment on microglia.
  • To elucidate the role of microglial cells in the progression of degenerative disc disease.

Main Methods:

  • Bovine caudal IVDs were cultured ex vivo under mechanical loading simulating degeneration or in free-swelling control conditions.
  • Conditioned media (CM) from IVDs were analyzed for cytokine and neurotrophin content.
  • Microglial cells were exposed to CM to assess neuroinflammatory activation, proliferation, and gene expression.

Main Results:

  • Degenerative CM (D-CM) significantly increased the production of IL-8, NGF, IFN-γ, and IL-17 by IVD cells compared to control.
  • D-CM stimulated microglia proliferation, activation (increased IBA1, CD68 expression), and chemotaxis.
  • Microglia exposed to D-CM showed upregulation of genes including IL-1β, IL-6, TNFα, iNOS, IBA1, and VEGF.

Conclusions:

  • The neuroinflammatory microenvironment of degenerating IVDs activates microglia.
  • Activated microglia contribute to the inflammatory milieu within IVD tissues and surrounding areas.
  • Microglia play a crucial role in maintaining the neuroinflammatory state of IVDs and may contribute to low back pain.

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