Matrix metalloproteinase-13 expression in IL-1β-treated chondrocytes by activation of the p38 MAPK/c-Fos/AP-1 and JAK/STAT pathways

Arch Pharm Res. 2011 Jan;34(1):109-17. doi: 10.1007/s12272-011-0113-4. Epub 2011 Apr 6.


Matrix metalloproteinase-13 (MMP-13, mammalian collagenase) degrades the cartilage matrix in pathological conditions such as osteoarthritis. Here, to establish the signaling pathway to MMP-13 induction, effects of mitogen-activated protein kinase (MAPK) pathway and the possibility of some other signaling pathways involved are investigated in interleukin-1β (IL-1β)-treated human chondrosarcoma cell line, SW1353 cells. IL-1β (10 ng/mL) treatment induced MMP-13 in SW1353 cells, with concomitant activation of nuclear factor-κB, activator protein-1 (AP-1) and MAPKs, including extracellular signal-regulated protein kinase, p38 MAPK and c-Jun N-terminal kinase. Among these MAPKs, only p38 MAPK inhibitor (SB203580) blocked MMP-13 induction and AP-1 activation in IL-1β-treated SW1353 cells. SB203580 also inhibited c-Fos translocation to the nucleus (but not c-Jun). Importantly, IL-1β treatment induced Janus kinase 2 (JAK2) and signal transducer and activator of transcription 1/2 (STAT1/2) activation. The JAK2 inhibitor (AG490) blocked STAT1/2 activation as well as MMP-13 induction in IL-1β-treated SW1353 cells. STAT1/2 siRNA transfection also reduced MMP-13 expression levels. Thus, from the present study, it is concluded that p38 MAPK/c-Fos/AP-1 and JAK2/STAT1/2 are involved in MMP-13 induction of IL-1β-treated human chondrocytes, SW1353 cells. Blocking these signaling pathways may have chondroprotective effects in cartilage degeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Chondrosarcoma / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin-1beta / pharmacology*
  • Janus Kinases / metabolism
  • Matrix Metalloproteinase 13 / genetics*
  • Proto-Oncogene Proteins c-fos / drug effects
  • Proto-Oncogene Proteins c-fos / metabolism
  • STAT Transcription Factors / metabolism
  • Signal Transduction / drug effects*
  • Transcription Factor AP-1 / drug effects
  • Transcription Factor AP-1 / metabolism
  • p38 Mitogen-Activated Protein Kinases / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Interleukin-1beta
  • Proto-Oncogene Proteins c-fos
  • STAT Transcription Factors
  • Transcription Factor AP-1
  • Janus Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 13