Tohoku J. Exp. Med., 2000, 192 (2)

Effects of Bisphosphonate on the Release of MMP-2 from Cultured Human Osteoblasts

YASUFUMI ICHINOSE, KIYOSHI MIGITA, TOMOKI NAKASHIMA,1 ATSUSHI KAWAKAMI, TAKAHIKO AOYAGI2 and KATSUMI EGUCHI

The First Department of Internal Medicine, 1The Department of Hospital Pharmacy, Nagasaki University School of Medicine, Nagasaki 852-8501, and 2Department of Orthopedic Surgery, National Ureshino Hospital, Saga 843-0301

  • Production of matrix metalloproteinases (MMPs) influences bone resorption. We investigated the role of bisphosphonates, potent inhibitors of bone resorption, on the production of MMP-2 from human osteoblasts. Bisphosphonates alone did not influence the amount of MMP-2 produced by human osteoblasts. However, in the presence of physiological concentrations of plasmin, bisphosphonates reduced the amount of MMP-2 in osteoblasts-conditioned media. Furthermore, bisphosphonates treatment induced degradation of MMP-2 in the presence of plasmin. Our results indicated that bisphosphonate, a divalent cation chelator, negatively regulated the longevity of MMP-2 in soluble phase plasmin-containing environment. These findings suggest that bisphosphonates inhibit bone resorption by abrogating MMP-2 protection induced by plasmin-mediated degradation.
    Key words--- bisphosphonates; matrix metalloproteinases; osteoblast; plasmin
    © 2000 Tohoku University Medical Press

    Tohoku J. Exp. Med., 2000, 192, 111-118
    Address for reprints: Katsumi Eguchi, Chairman and Professor, The First Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto 1-7-1, Nagasaki 852-8501, Japan.
    e-mail: eguchi@net.nagasaki-u.ac.jp

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