Hyaluronate inhibits the interleukin-1beta-induced expression of matrix metalloproteinase (MMP)-1 and MMP-3 in human synovial cells

Tohoku J Exp Med. 2004 Oct;204(2):99-107. doi: 10.1620/tjem.204.99.


Intra-articular administration of hyaluronate (HA) is an effective treatment for arthritis. HA injections can decrease not only joint pain but also synovial effusion, although little is known concerning the mechanism of HA action. The aim of this study was to investigate the role of HA on the expression and production of matrix metalloproteinase (MMP) in synovial cells activated by interleukin (IL)-1beta in order to achieve a better understanding of exogenous HA function in the extracellular matrix degradation in arthritic joints. Human synovial cells were incubated with HA (0.1-1000 microg/ml) and/or IL-1beta (1 ng/ml). The expression of MMP-1 and MMP-3 mRNAs was analyzed by quantitative real-time polymerase chain reaction. The protein levels of MMP-1 and MMP-3 in cultured media were measured by immunoblotting. Expression of MMP-1 and MMP-3 mRNAs was induced by IL-1beta. The IL-1beta-mediated induction of MMP-1 mRNA expression was attenuated by 10 microg/ml HA (p=0.026) and that of MMP-3 mRNA was strongly down-regulated in the presence of 10 or 1000 microg/ml HA (p<0.001). The increased protein levels of MMP-1 and MMP-3 were also reduced by 1000 microg/ml HA. These data suggest that HA inhibits the expression and production of MMP-1 and MMP-3 in IL-1beta-stimulated human synovial cells. We therefore prepose that intra-articular HA may rescue inflamed joints from bone and cartilage destruction by reducing the production of MMP-1 and MMP-3.

MeSH terms

  • Cells, Cultured
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Humans
  • Hyaluronic Acid / pharmacology*
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / pharmacology*
  • Kinetics
  • Matrix Metalloproteinase 1 / genetics*
  • Matrix Metalloproteinase 3 / genetics*
  • RNA, Messenger / genetics
  • Stromal Cells / cytology
  • Stromal Cells / drug effects
  • Stromal Cells / enzymology
  • Stromal Cells / immunology
  • Synovial Membrane / cytology
  • Synovial Membrane / drug effects
  • Synovial Membrane / enzymology*
  • Synovial Membrane / immunology


  • Interleukin-1
  • RNA, Messenger
  • Hyaluronic Acid
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 1