Effects of nitric oxide on matrix metalloproteinase-2 production by rheumatoid synovial cells

Life Sci. 2001 Jan 12;68(8):913-20. doi: 10.1016/s0024-3205(00)00998-x.


Nitric oxide (NO) is a multifunctional messenger molecule generated from L-arginine by a family of enzymes, including nitric oxide synthase (NOS). This study was performed to examine whether NO modulates the production of matrix metalloproteinases (MMPs), which degrade all components of extracellular matrix (ECM), in rheumatoid synovial cells. We investigated the effects of exogenously generated NO by a NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), on the MMPs production by rheumatoid synovial cells. Culture media conditioned by SNAP-treated synovial cells were examined by gelatin zymography and immunoblot analysis. Incubation of synovial cells with SNAP resulted in gelatinase A production in a dose-dependent fashion. Furthermore, RT-PCR analysis demonstrated that MMP-2 mRNA expression was induced in SNAP-treated synovial cells. In contrast, SNAP did not influence the production of TIMP-1 and TIMP-2, which preferentially inhibit MMP-2, by rheumatoid synovial cells. Our data indicate that NO could modulate MMP production by rheumatoid synovial cells and therefore contribute to ECM degradation of articular components in RA.

MeSH terms

  • Arthritis, Rheumatoid / enzymology*
  • Arthritis, Rheumatoid / pathology
  • Cell Culture Techniques
  • Culture Media, Conditioned
  • Humans
  • Matrix Metalloproteinase 2 / biosynthesis*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase Inhibitors
  • Nitric Oxide / pharmacology*
  • Nitric Oxide Donors / pharmacology
  • Osteoarthritis / enzymology
  • Osteoarthritis / pathology
  • Penicillamine / analogs & derivatives
  • Penicillamine / pharmacology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • S-Nitroso-N-Acetylpenicillamine
  • Synovial Membrane / enzymology*
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis
  • Tissue Inhibitor of Metalloproteinase-2 / biosynthesis


  • Culture Media, Conditioned
  • Matrix Metalloproteinase Inhibitors
  • Nitric Oxide Donors
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Nitric Oxide
  • S-Nitroso-N-Acetylpenicillamine
  • Matrix Metalloproteinase 2
  • Penicillamine