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

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7 Citations (Scopus)

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

Fingerprint

Intervertebral Disc
Metalloproteases
Extracellular Matrix
Matrix Metalloproteinase 1
Vascular Cell Adhesion Molecule-1
Conditioned Culture Medium
Interleukin-1
Vascular Endothelial Growth Factor A
Cell Hypoxia
Matrix Metalloproteinase 3
Interleukin-8
Interleukin-6
Macrophages
Hypoxia-Inducible Factor 1
Angiogenesis Inducing Agents
Transcriptional Activation
Hypoxia
Transcription Factors
Western Blotting
Enzyme-Linked Immunosorbent Assay

Keywords

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

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

@article{fbce2f40a01240b19868403dd502869f,
title = "The role of hypoxia in angiogenesis and extracellular matrix regulation of intervertebral disc cells during inflammatory reactions",
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 na{\"i}ve 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.",
keywords = "Annulus fibrosus, ECM regulating enzymes, Hypoxia, Inflammation, Inflammatory mediators, Nucleus pulposus",
author = "Kwon, {Woo Keun} and Moon, {Hong Joo} and Taek-Hyun Kwon and Youn-Kwan Park and Joo-Han Kim",
year = "2017",
month = "11",
day = "1",
doi = "10.1093/neuros/nyx149",
language = "English",
volume = "81",
pages = "867--875",
journal = "Neurosurgery",
issn = "0148-396X",
publisher = "Lippincott Williams and Wilkins",
number = "5",

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TY - JOUR

T1 - The role of hypoxia in angiogenesis and extracellular matrix regulation of intervertebral disc cells during inflammatory reactions

AU - Kwon, Woo Keun

AU - Moon, Hong Joo

AU - Kwon, Taek-Hyun

AU - Park, Youn-Kwan

AU - Kim, Joo-Han

PY - 2017/11/1

Y1 - 2017/11/1

N2 - 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.

AB - 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.

KW - Annulus fibrosus

KW - ECM regulating enzymes

KW - Hypoxia

KW - Inflammation

KW - Inflammatory mediators

KW - Nucleus pulposus

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U2 - 10.1093/neuros/nyx149

DO - 10.1093/neuros/nyx149

M3 - Article

C2 - 28475716

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VL - 81

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JO - Neurosurgery

JF - Neurosurgery

SN - 0148-396X

IS - 5

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