The role of hypoxia in angiogenesis and extracellular matrix regulation of intervertebral disc cells during inflammatory reactions

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Abstract

Background: The intervertebral disc (IVD) is an avascular structure, and is therefore stable under hypoxic conditions. Previous studies have demonstrated that hypoxia might be related to symptomatic degenerative disc diseases (DDDs); however, the pathomechanism is still poorly understood. Objective: To identify the effect of hypoxia on the production of inflammatory mediators, angiogenic factors, and extracellularmatrix-regulating enzymes of IVD cells during inflammatory reactions. Methods: Human nucleus pulposus (NP) and annulus fibrosus (AF) cells harvested during surgery for DDDs were cultured in macrophage conditioned media or interleukin (IL)-1β-stimulated media under hypoxic (2%) and normoxic (21%) conditions. Hypoxiainducible factor-1α transcription factor activation was analyzed by western blotting. IL-6, IL-8, vascular endothelial growth factor (VEGF), vascular cell adhesion molecule (VCAM), matrix metalloproteinase (MMP)-1, MMP-3, tissue inhibitor of metalloprotease (TIMP)-1, and TIMP-2 in conditioned media weremeasured by an enzyme-linked immunosorbent assay. Results: NP cells expressed higher hypoxia-inducible factor-1α in the IL-1β-stimulated group under hypoxic condition. MMP-1 was significantly increased in the AF cells under hypoxic condition; TIMP-1 and TIMP-2 were significantly decreased in both naïve NP and AF cells during hypoxia. Both cells in macrophage conditioned media significantly diminished the production of IL-6 and VCAM, while VEGF significantly increased during hypoxia. After 1 ng/mL IL-1β stimulation, IL-8, VEGF, MMP-1, and MMP-3 were significantly increased in both cell types during hypoxia, while VCAM, TIMP-1, and TIMP-2 were decreased. Conclusion: We found that hypoxia can enhance the angiogenic ability of IVD during inflammatory reactions, and cause progress in development of DDD via extracellular matrix regulation in this in vitro study.

Original languageEnglish
Pages (from-to)867-875
Number of pages9
JournalClinical Neurosurgery
Volume81
Issue number5
DOIs
Publication statusPublished - 2017 Nov 1

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Keywords

  • Annulus fibrosus
  • ECM regulating enzymes
  • Hypoxia
  • Inflammation
  • Inflammatory mediators
  • Nucleus pulposus

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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