Effects of bisphosphonate on the release of MMP-2 from cultured human osteoblasts.
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.
Ichinose
Y
Y
The First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Migita
K
K
Nakashima
T
T
Kawakami
A
A
Aoyagi
T
T
Eguchi
K
K
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*
D000911:Antibodies, Monoclonal; D004164:Diphosphonates; D005341:Fibrinolysin; D020778:Matrix Metalloproteinase 2