Tohoku J. Exp. Med., 2004, 204(2)

Hyaluronate Inhibits the Interleukin-1β-Induced Expression of Matrix Metalloproteinase (MMP)-1 and MMP-3 in Human Synovial Cells

AKIKO SASAKI, KAN SASAKI, YRJÖ T. KONTTINEN,¹ SEPPO SANTAVIRTA,² MASATOSHI TAKAHARA, HIROSHI TAKEI, TOSHIHIKO OGINO and MICHIAKI TAKAGI

Department of Orthopedic Surgery, Yamagata University School of Medicine, Yamagata, Japan,
¹Invärtes Medicine, Helsinki University Central Hospital, ORTON Orthopedic Hospital, Invalid Foundation, Helsinki, Finland, and
²Department of Orthopedics and Traumatology, Helsinki University Central Hospital, Helsinki, Finland

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)-1β 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 μg/ml) and/or IL-1β (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-1β. The IL-1β-mediated induction of MMP-1 mRNA expression was attenuated by 10 μg/ml HA (p=0.026) and that of MMP-3 mRNA was strongly down-regulated in the presence of 10 or 1000 μg/ml HA (p<0.001). The increased protein levels of MMP-1 and MMP-3 were also reduced by 1000 μg/ml HA. These data suggest that HA inhibits the expression and production of MMP-1 and MMP-3 in IL-1β-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.

keywords —— Hyaluronate; interleukin-1β; human synovial cells; matrix metalloproteinases; tissue inhibitor of metalloproteinases

© 2004 Tohoku University Medical Press

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Address for reprint: Akiko Sasaki, M.D., Department of Orthopaedic Surgery, Yamagata University School of Medicine, 2-2-2 Iida Nishi, Yamagata 990-9585, Japan.

e-mail: aksasaki@med.id.yamagata-u.ac.jp