OSTEONECTIN IN MATRIX REMODELING - A PLASMINOGEN-OSTEONECTIN-COLLAGENCOMPLEX

Osteonectin is an adhesive glycoprotein synthesized constitutively by osteoblasts, endothelial cells, and megakaryocytes. Bone-derived and p latelet derived osteonectins differ in their electrophoretic mobility and carbohydrate content, and each displays different affinities for c ollagen matrices. Both types of osteonectin bind to plasminogen (K-d(a pp), of 4.7 +/- 1.0 x 10(-8) M for bone osteonectin and 1.2 +/- 0.1 x 10(-7) M for platelet osteonectin). The osteonectin plasminogen intera ction is inhibited by alpha(2)-antiplasmin and E aminocaproic acid, su ggesting that the interaction is mediated through the kringle 1 region of plasminogen. Both osteonectins enhance the rate of plasmin generat ion by tissue-type plasminogen activator to approximately the same ext ent as fibrinogen. Equilibrium binding measurements conducted using to tal internal reflection fluorescence spectroscopy indicate that plasmi nogen binds to collagen in the presence of bone osteonectin (K-d = 1.3 0 +/- 0.1 x 10(-7) M). No binding of plasminogen to collagen matrix wa s detected in the presence of platelet osteonectin or in the absence o f bone osteonectin. Bone osteonectin-dependent binding of plasminogen to collagen matrix: is reversed by the addition of epsilon-aminocaproi c acid. The ability of both types of osteonectin to bind to and influe nce plasminogen activation and of bone osteonectin to anchor plasminog en on collagen matrices suggests that osteonectin may play a role in d irecting extracellular matrix proteolysis.