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The Effects of TWEAK, Fn14, and TGF-beta1 on Degeneration of Human Intervertebral Disc

Hoon Huh1, Yong-Jik Lee, Jung-Hee Kim

  • 1Department of Neurosurgery, Medical Institute, Seoul Medical Center, Seoul, Korea.

Journal of Korean Neurosurgical Society
|February 17, 2010
PubMed
Abstract

Insights

Tumor necrosis factor (TNF) like weak inducer of apoptosis (TWEAK) significantly decreases sulfated glycosaminoglycan (sGAG) and key gene expression in human intervertebral disc (IVD) degeneration. Fibroblast growth factor-inducible 14 (Fn14) and transforming growth factor-beta1 (TGF-beta1) partially counteract TWEAK's effects.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Biomedical Engineering

Background:

  • Intervertebral disc (IVD) degeneration is a complex process.
  • The roles of specific molecular mediators like TWEAK, Fn14, and TGF-beta1 in IVD degeneration require further elucidation.

Purpose of the Study:

  • To investigate the effects of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), fibroblast growth factor-inducible 14 (Fn14), and transforming growth factor-beta1 (TGF-beta1) on human IVD degeneration.
  • To understand the reciprocal actions of these factors in modulating IVD cellular and matrix components.

Main Methods:

  • Human IVD tissues and cells were cultured in vitro.
  • Levels of sulfated glycosaminoglycan (sGAG) were measured using dimethyl methyleneblue (DMMB) assay.
  • Messenger RNA (mRNA) levels of sex determining region Y (SRY)-box 9 (Sox9) and versican were quantified via reverse transcriptase polymerase chain reaction (RT-PCR).

Main Results:

  • TWEAK significantly decreased sGAG content and mRNA levels of versican and Sox9 in IVD tissues.
  • TGF-beta1 increased sGAG concentration and Sox9 mRNA expression.
  • Fn14 did not significantly alter sGAG production but showed a trend towards increasing sGAG and gene expression when combined with TGF-beta1.

Conclusions:

  • TWEAK plays a role in intervertebral disc degeneration by reducing sGAG and key matrix gene expression.
  • TGF-beta1 may have protective effects, partially counteracting TWEAK-induced degeneration.
  • Further research is needed to fully understand the therapeutic potential of modulating these pathways in IVD disorders.
Keywords:
Fn14Intervertebral discSox9TGF-β1TWEAKVersican

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