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

• Published in: The Tohoku Journal of Experimental Medicine Vol. 192; no. 2; pp. 111 - 118
• Main Authors: Ichinose, Yasufumi, Migita, Kiyoshi, Nakashima, Tomoki, Kawakami, Atsushi, Aoyagi, Takahiko, Eguchi, Katsumi
• Format: Journal Article
• Language: English
• Published: Japan Tohoku University Medical Press 01.10.2000
• Subjects: Antibodies, Monoclonal; bisphosphonates; Cells, Cultured; Diphosphonates - pharmacology; Extracellular Matrix - metabolism; Fibrinolysin - metabolism; Fibrinolysin - pharmacology; Humans; Immunoblotting; Matrix Metalloproteinase 2 - immunology; Matrix Metalloproteinase 2 - metabolism; matrix metalloproteinases; osteoblast; Osteoblasts - metabolism; plasmin
• ISSN: 0040-8727; 1349-3329
• DOI: 10.1620/tjem.192.111

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.