Matrix degradative enzymes and their inhibitors during annular inflammation

Initial step of symptomatic intervertebral disc degeneration

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective: Symptomatic disc degeneration develops from inflammatory reactions in the annulus fibrosus (AF). Although inflammatory mediators during annular inflammation have been studied, the roles of matrix metalloproteinases (MMPs) and their inhibitors have not been fully elucidated. In this study, we evaluated the production of MMPs and tissue inhibitors of metalloproteinase (TIMPs) during annular inflammation using an in vitro co-culture system. We also examined the effect of notochordal cells on annular inflammation. Methods: Human AF (hAF) pellet was co-cultured for 48 hours with phorbol myristate acetate-stimulated macrophage-like THP-1 cells. hAF pellet and conditioned media (CM) from co-cultured cells were assayed for MMPs, TIMPs, and insulin-like growth factor (IGF)-1 levels using real-time reverse-transcriptase polymerase chain reaction and enzyem-linked immunosorbent assay. To evaluate whether notochordal cells affected MMPs or TIMPs production on annular inflammation, hAF co-cultured with notochordal cells from adult New Zealand White rabbits, were assayed. Results: MMP-1, -3, -9; and TIMP-1 levels were significantly increased in CM of hAF co-cultured with macrophage-like cells compared with hAF alone, whereas TIMP-2 and IGF-1 levels were significantly decreased (p<0.05). After macrophage exposure, hAF produced significantly more MMP-1 and -3 and less TIMP-1 and -2. Interleukin-1β stimulation enhanced MMP-1 and -3 levels, and significantly diminished TIMP-2 levels. Co-culturing with rabbit notochordal cells did not significantly influence MMPs and TIMPs production or COL1A2 gene expression. Conclusion: Our results indicate that macrophage-like cells evoke annular degeneration through the regulation of major degradative enzymes and their inhibitors, produced by hAF, suggesting that the selective regulation of these enzymes provides future targets for symptomatic disc degeneration therapy.

Original languageEnglish
Pages (from-to)237-243
Number of pages7
JournalJournal of Korean Neurosurgical Society
Volume55
Issue number5
DOIs
Publication statusPublished - 2014 Jan 1

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Intervertebral Disc Degeneration
Enzyme Inhibitors
Tissue Inhibitor of Metalloproteinases
Matrix Metalloproteinase Inhibitors
Inflammation
Tissue Inhibitor of Metalloproteinase-2
Matrix Metalloproteinase 3
Matrix Metalloproteinase 1
Macrophages
Tissue Inhibitor of Metalloproteinase-1
Somatomedins
Conditioned Culture Medium
Rabbits
Immunosorbents
Tetradecanoylphorbol Acetate
Coculture Techniques
Reverse Transcriptase Polymerase Chain Reaction
Matrix Metalloproteinases
Interleukin-1
Real-Time Polymerase Chain Reaction

Keywords

  • Annular inflammation
  • IGF-1
  • Matrix metalloproteinase
  • Notochordal cells
  • Symptomatic intervertebral disc degeneration
  • Tissue inhibitor of metalloproteinase

ASJC Scopus subject areas

  • Surgery
  • Neuroscience(all)
  • Clinical Neurology

Cite this

@article{a960b685668d4db3b6e39202dfaedd78,
title = "Matrix degradative enzymes and their inhibitors during annular inflammation: Initial step of symptomatic intervertebral disc degeneration",
abstract = "Objective: Symptomatic disc degeneration develops from inflammatory reactions in the annulus fibrosus (AF). Although inflammatory mediators during annular inflammation have been studied, the roles of matrix metalloproteinases (MMPs) and their inhibitors have not been fully elucidated. In this study, we evaluated the production of MMPs and tissue inhibitors of metalloproteinase (TIMPs) during annular inflammation using an in vitro co-culture system. We also examined the effect of notochordal cells on annular inflammation. Methods: Human AF (hAF) pellet was co-cultured for 48 hours with phorbol myristate acetate-stimulated macrophage-like THP-1 cells. hAF pellet and conditioned media (CM) from co-cultured cells were assayed for MMPs, TIMPs, and insulin-like growth factor (IGF)-1 levels using real-time reverse-transcriptase polymerase chain reaction and enzyem-linked immunosorbent assay. To evaluate whether notochordal cells affected MMPs or TIMPs production on annular inflammation, hAF co-cultured with notochordal cells from adult New Zealand White rabbits, were assayed. Results: MMP-1, -3, -9; and TIMP-1 levels were significantly increased in CM of hAF co-cultured with macrophage-like cells compared with hAF alone, whereas TIMP-2 and IGF-1 levels were significantly decreased (p<0.05). After macrophage exposure, hAF produced significantly more MMP-1 and -3 and less TIMP-1 and -2. Interleukin-1β stimulation enhanced MMP-1 and -3 levels, and significantly diminished TIMP-2 levels. Co-culturing with rabbit notochordal cells did not significantly influence MMPs and TIMPs production or COL1A2 gene expression. Conclusion: Our results indicate that macrophage-like cells evoke annular degeneration through the regulation of major degradative enzymes and their inhibitors, produced by hAF, suggesting that the selective regulation of these enzymes provides future targets for symptomatic disc degeneration therapy.",
keywords = "Annular inflammation, IGF-1, Matrix metalloproteinase, Notochordal cells, Symptomatic intervertebral disc degeneration, Tissue inhibitor of metalloproteinase",
author = "Joo-Han Kim and Park, {Jin Hyun} and Moon, {Hong Joo} and Taek-Hyun Kwon and Youn-Kwan Park",
year = "2014",
month = "1",
day = "1",
doi = "10.3340/jkns.2014.55.5.237",
language = "English",
volume = "55",
pages = "237--243",
journal = "Journal of Korean Neurosurgical Society",
issn = "2005-3711",
publisher = "Daehan sin'gyeong oe'gwa haghoe",
number = "5",

}

TY - JOUR

T1 - Matrix degradative enzymes and their inhibitors during annular inflammation

T2 - Initial step of symptomatic intervertebral disc degeneration

AU - Kim, Joo-Han

AU - Park, Jin Hyun

AU - Moon, Hong Joo

AU - Kwon, Taek-Hyun

AU - Park, Youn-Kwan

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Objective: Symptomatic disc degeneration develops from inflammatory reactions in the annulus fibrosus (AF). Although inflammatory mediators during annular inflammation have been studied, the roles of matrix metalloproteinases (MMPs) and their inhibitors have not been fully elucidated. In this study, we evaluated the production of MMPs and tissue inhibitors of metalloproteinase (TIMPs) during annular inflammation using an in vitro co-culture system. We also examined the effect of notochordal cells on annular inflammation. Methods: Human AF (hAF) pellet was co-cultured for 48 hours with phorbol myristate acetate-stimulated macrophage-like THP-1 cells. hAF pellet and conditioned media (CM) from co-cultured cells were assayed for MMPs, TIMPs, and insulin-like growth factor (IGF)-1 levels using real-time reverse-transcriptase polymerase chain reaction and enzyem-linked immunosorbent assay. To evaluate whether notochordal cells affected MMPs or TIMPs production on annular inflammation, hAF co-cultured with notochordal cells from adult New Zealand White rabbits, were assayed. Results: MMP-1, -3, -9; and TIMP-1 levels were significantly increased in CM of hAF co-cultured with macrophage-like cells compared with hAF alone, whereas TIMP-2 and IGF-1 levels were significantly decreased (p<0.05). After macrophage exposure, hAF produced significantly more MMP-1 and -3 and less TIMP-1 and -2. Interleukin-1β stimulation enhanced MMP-1 and -3 levels, and significantly diminished TIMP-2 levels. Co-culturing with rabbit notochordal cells did not significantly influence MMPs and TIMPs production or COL1A2 gene expression. Conclusion: Our results indicate that macrophage-like cells evoke annular degeneration through the regulation of major degradative enzymes and their inhibitors, produced by hAF, suggesting that the selective regulation of these enzymes provides future targets for symptomatic disc degeneration therapy.

AB - Objective: Symptomatic disc degeneration develops from inflammatory reactions in the annulus fibrosus (AF). Although inflammatory mediators during annular inflammation have been studied, the roles of matrix metalloproteinases (MMPs) and their inhibitors have not been fully elucidated. In this study, we evaluated the production of MMPs and tissue inhibitors of metalloproteinase (TIMPs) during annular inflammation using an in vitro co-culture system. We also examined the effect of notochordal cells on annular inflammation. Methods: Human AF (hAF) pellet was co-cultured for 48 hours with phorbol myristate acetate-stimulated macrophage-like THP-1 cells. hAF pellet and conditioned media (CM) from co-cultured cells were assayed for MMPs, TIMPs, and insulin-like growth factor (IGF)-1 levels using real-time reverse-transcriptase polymerase chain reaction and enzyem-linked immunosorbent assay. To evaluate whether notochordal cells affected MMPs or TIMPs production on annular inflammation, hAF co-cultured with notochordal cells from adult New Zealand White rabbits, were assayed. Results: MMP-1, -3, -9; and TIMP-1 levels were significantly increased in CM of hAF co-cultured with macrophage-like cells compared with hAF alone, whereas TIMP-2 and IGF-1 levels were significantly decreased (p<0.05). After macrophage exposure, hAF produced significantly more MMP-1 and -3 and less TIMP-1 and -2. Interleukin-1β stimulation enhanced MMP-1 and -3 levels, and significantly diminished TIMP-2 levels. Co-culturing with rabbit notochordal cells did not significantly influence MMPs and TIMPs production or COL1A2 gene expression. Conclusion: Our results indicate that macrophage-like cells evoke annular degeneration through the regulation of major degradative enzymes and their inhibitors, produced by hAF, suggesting that the selective regulation of these enzymes provides future targets for symptomatic disc degeneration therapy.

KW - Annular inflammation

KW - IGF-1

KW - Matrix metalloproteinase

KW - Notochordal cells

KW - Symptomatic intervertebral disc degeneration

KW - Tissue inhibitor of metalloproteinase

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DO - 10.3340/jkns.2014.55.5.237

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JF - Journal of Korean Neurosurgical Society

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