c-Jun N-terminal kinase and nuclear factor κB mediate nitric oxide-induced expression of matrix metalloproteinase-13

Int Orthop. 2011 Aug;35(8):1261-6. doi: 10.1007/s00264-010-1056-y. Epub 2010 Jun 4.

Abstract

The purpose of this study was to investigate the mechanism of expression of matrix metalloproteinase-13 (MMP-13) induced by nitric oxide (NO). Human chondrocytes (HCs) were stimulated with a NO donor (MAHMA-NONOate), then mitogen-activated protein kinases' (MAPKs) and nuclear factor κB' (NF-κB) activations and MMP-13' expression were assayed by Western blot analysis. Additionally, the intracellular signalling of NO was investigated using the inhibitors of MAPKs and NF-κB. NO-induced MMP-13 expression was not suppressed by extracellular signal-regulated kinase (ERK) inhibitor (PD98059) or inhibitors of p38 kinase (SB203580), but was inhibited by a c-jun terminal kinase (JNK) inhibitor (SP600125) and inhibitors of NF-κB (SN-50). Additionally, SP600125 treatment reduced NF-κB activation, but SN-50 treatment did not significantly affect JNK activation. These results suggest that NO induces MMP-13 expression by JNK and NF-κB activation in HCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cartilage, Articular / cytology
  • Cartilage, Articular / drug effects
  • Cells, Cultured
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism*
  • Enzyme Induction / physiology
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Hydrazines / pharmacology
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Matrix Metalloproteinase 13 / metabolism*
  • Matrix Metalloproteinase Inhibitors
  • NF-kappa B / metabolism*
  • Nitric Oxide / metabolism*

Substances

  • 1-hexanamine-6-(2-hydroxy-1-methyl-2-nitrosohydrazine)-N-methyl
  • Enzyme Inhibitors
  • Hydrazines
  • Matrix Metalloproteinase Inhibitors
  • NF-kappa B
  • Nitric Oxide
  • JNK Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 13