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.