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The c-FOS Protein Immunohistological Detection: A Useful Tool As a Marker of Central Pathways Involved in Specific Physiological Responses In Vivo and Ex Vivo
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C-Fos regulation by the MAPK and PKC pathways in intervertebral disc cells

Katsuya Yokoyama1, Akihiko Hiyama, Fumiyuki Arai

  • 1Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine, Kanagawa, Japan ; Research Center for Regenerative Medicine, Tokai University School of Medicine, Kanagawa, Japan.

Plos One
|September 12, 2013
PubMed
Abstract

Insights

This study reveals opposing roles for MAPK and PKC pathways in regulating c-fos expression within intervertebral disc cells. Understanding these signals may offer new strategies for managing joint disease.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The gene c-fos is implicated in joint disease pathogenesis.
  • Its role and signaling mechanisms in intervertebral disc (IVD) cells remain unclear.
  • This study investigates c-fos activation via mitogen-activated protein kinases (MAPKs) and protein kinase C (PKC) in nucleus pulposus (NP) cells.

Purpose of the Study:

  • To investigate the involvement of MAPK and PKC signaling pathways in the regulation of c-fos expression in NP cells.
  • To determine the functional impact of c-fos on extracellular matrix gene expression in NP cells.
  • To elucidate the opposing effects of MAPK and PKC pathways on c-fos regulation.

Main Methods:

  • Gene expression analysis using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting.
  • Transfection experiments to assess c-fos activity and its impact on target genes.
  • Cell viability assays (MTT) and pathway inhibition using specific kinase inhibitors (PD98059, SKF86002, SB202190, SP600125).

Main Results:

  • Phorbol 12-myristate 13-acetate (PMA) induced c-fos transcription and protein expression, activating MAPK pathways.
  • MAPK inhibition via PD98059 suppressed c-fos promoter activity.
  • PKC isoforms (PKCγ and PKCδ) suppressed c-fos promoter activity, indicating opposing pathway effects.
  • Overexpression of c-fos inhibited aggrecan and Col2 gene expression.

Conclusions:

  • The MAPK and PKC pathways exert opposing regulatory effects on c-fos in NP cells.
  • c-fos expression can be suppressed within the extracellular matrix of NP cells.
  • These findings provide novel insights into the molecular mechanisms underlying IVD degeneration.

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