Alendronate promotes plasmin-mediated MMP-9 inactivation by exposing cryptic plasmin degradation sites within the MMP-9 catalytic domain

► We report the inhibitory effect of plasmin in the presence of Alendronate upon proMMP-9. ► Alendronate promotes non-reversible plasmin-mediated MMP-9 inactivation. ► Alendronate plus plasmin degrades MMP-9 to inactive catalytic site and hemopexin-domain fragments. ► Hemopexin-domain generated by plasmin plus Alendronate inhibits MMP-9 activity. ► New rational for Alendronate use in MMP-9/plasmin-dependent pathology.