title: Effects of bisphosphonate on the release of MMP-2 from cultured human osteoblasts.
abstract: 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.
authors.affiliation: The First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ichinose
authors.forename: K
authors.initials: K
authors.lastname: Migita
authors.forename: T
authors.initials: T
authors.lastname: Nakashima
authors.forename: A
authors.initials: A
authors.lastname: Kawakami
authors.forename: T
authors.initials: T
authors.lastname: Aoyagi
authors.forename: K
authors.initials: K
authors.lastname: Eguchi
mesh_terms: D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D004164:Diphosphonates / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D020778:Matrix Metalloproteinase 2 / Q000276:immunology / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D004164:Diphosphonates; D005341:Fibrinolysin; D020778:Matrix Metalloproteinase 2