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Matrix metalloproteinase (MMP)-12 regulates MMP-9 expression in interleukin-1beta-treated articular chondrocytes

Hwanhee Oh1, Siyoung Yang, Meeyoung Park

  • 1Department of Life Science, Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, South Korea.

Journal of Cellular Biochemistry
|November 5, 2008
PubMed

Insights

Interleukin-1beta stimulates matrix metalloproteinase (MMP)-12 in chondrocytes via MAP kinase pathways. MMP-12 then enhances the expression and activation of MMP-9, suggesting a role in cartilage regulation.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Matrix metalloproteinase (MMP)-12's role in chondrocytes is largely unknown.
  • Chondrocytes are key cells in cartilage maintenance and degradation.

Purpose of the Study:

  • To investigate the expression and function of MMP-12 in chondrocytes.
  • To elucidate the signaling pathways regulating MMP-12 in chondrocytes.
  • To determine MMP-12's influence on other MMPs, particularly MMP-9.

Main Methods:

  • Primary chondrocyte cultures and cartilage explants were utilized.
  • Interleukin (IL)-1beta was used to stimulate chondrocytes.
  • Mitogen-activated protein (MAP) kinase pathways were analyzed for involvement in MMP-12 regulation.
  • Expression and activation levels of MMP-12 and MMP-9 were assessed.

Main Results:

  • IL-1beta induced both the expression and activation of MMP-12 in chondrocytes.
  • Extracellular signal-regulated kinase and p38 kinase pathways were essential for MMP-12 expression.
  • c-jun N-terminal kinase was required for MMP-12 activation.
  • MMP-12 alone did not affect other MMPs, but it enhanced IL-1beta-induced MMP-9 expression and activation.

Conclusions:

  • IL-1beta induces MMP-12 expression and activation in chondrocytes through MAP kinase signaling.
  • Activated MMP-12 potentiates the expression and activation of MMP-9 in chondrocytes.
  • These findings suggest MMP-12 plays a regulatory role in chondrocyte function and potentially cartilage degradation.

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