Collagen breakdown in soft connective tissue explants is associated with the level of active gelatinase A(MMP-2) but not with collagenase

Recent data suggest that gelatinase A (matrix metalloproteinase-2, MMP-2) p lays an important role in the degradation of collagen of soft connective ti ssues, In an attempt to investigate its participation in more detail we ass essed the digestion of collagen in cultured rabbit periosteal explants and compared this with the level of active MMP-2 and collagenases. The data dem onstrated that both collagen degradation and MMP activity increased with ti me. Conditioned medium obtained from explants cultured for 72 h showed that the level of active MMP-2 correlated with collagen degradation (r = 0.80, d.f. = 23, P < 0.0001). Such a relationship was not found with collagenase activity (r = -0.08, d.f. = 21, NS). The possible involvement of MMP-2 in c ollagen degradation was investigated further by incubating explants with se lective gelatinase inhibitors (CT1166, CT1399 and CT1746). In the presence of these compounds breakdown of collagen was almost completely abolished (a pproximate to 80%). Finally we assessed whether periosteal fibroblasts had the capacity to degrade collagen type I that conferred resistance to collag enase activity. Breakdown of this collagen did not differ from degradation of normal collagen. Taken together, our data provide support for the view t hat MMP-2 plays a crucial role in collagen degradation of soft connective t issue. (C) 1999 Elsevier Science B.V./International Society of Matrix Biolo gy. All rights reserved.