Evidence for an extracellular plasmin-dependent proteolytic system in mineralizing matrices.
Plasminogen activator, which specifically catalyzes the extracellular conversion of plasminogen to plasmin, was identified in the cell-free mineralizing matrices of enamel, dentin, cementum, and bone by a fibrinolytic overlay technique. The spatial separation in developing teeth of successive stages of dentinogenesis allowed us to identify predentin as a major site of plasminogen activator activity. In addition, plasminogen, the natural substrate for the activator, was demonstrated in predentin by immunohistochemical techniques. Extraction of human dentin/predentin with neutral demineralizing buffers solubilized the activator along with inhibitory components capable of blocking the activation of plasminogen. When resolved by polyacrylamide electrophoresis under dissociative conditions, however, the activator emerged in active form as two closely spaced bands at Mr 66,000 and 62,000. In the mineralizing enamel matrix of continuously forming rodent incisors, activator activity was limited to a 3-5 mm wide segment which marks the transition between "soft" and "chalky" enamel, whereas the entire overlying enamel organ was rich in activator activity at all developmental stages. This suggests that the activator is transported to the enamel matrix only in a narrow zone which coincides with the most rapidly mineralizing site. The coincident expression of plasminogen activator activity and mineral accretion suggests that plasmin-dependent proteolysis may play a role in the extracellular regulation of matrix mineralization.
D000818:Animals; D001857:Bone Matrix / Q000378:metabolism*; D003743:Dental Enamel / Q000378:metabolism; D003804:Dentin / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D008964:Molar, Third / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014070:Tooth / Q000378:metabolism
D010447:Peptide Hydrolases; D010960:Plasminogen Activators; D005341:Fibrinolysin