THE MEMBRANE-TYPE-MATRIX METALLOPROTEINASE MATRIX METALLOPROTEINASE-2TISSUE INHIBITOR OF METALLOPROTEINASE-2 SYSTEM IN PERIPROSTHETIC CONNECTIVE-TISSUE REMODELING IN LOOSE TOTAL-HIP PROSTHESES

The aim of the present study was to investigate the proteolytic potent ial and localization of matrix metalloproteinase (MMP)-2 in relation t o its regulatory protein, membrane-type-MMP (MT1-MMP), and tissue inhi bitor of metalloproteinase-e (TIMP-2), as well as to clarify an import ant step in the cascade of periprosthetic connective-tissue remodeling in loose total-hip prostheses. Immunohistochemical analysis revealed increased expression of MT1-MMP, MMP-2, and TIMP-2 in fibroblasts, syn ovial lining-like cells, and endothelial cells, as well as, to some ex tent, in monocyte/macrophage-like cells in both tissues from the bone- implant interface and reactive cellular tissues from regenerating caps ules in loose hip joints, when compared with control fibrous tissues b etween bone and implants retrieved from unloosened hip joints. In loos e hip joints, reverse transcription-PCR analysis showed the presence o f MT1-MMP, MMP-2, and TIMP-2 mRNA in both the bone-implant interface a nd regenerating capsular tissues. Increased protein levels of MMP-2 an d TIMP-2 were also demonstrated by an ELISA, and those of MT1-MMP were shown by immunoblot analysis. Gelatin-zymographic analysis confirmed the presence of both pro- and active forms of MMP-2, which suggested t he in situ activation of MMP-2 by MTI-MMP in the loose hip joints. Col lectively, these data suggest that the MT1-MMP/MMP-2/TIMP-2 system par ticipates in the extracellular matrix degradation and periprosthetic c onnective-tissue remodeling in loose hip joints, and may thus contribu te to the periprosthetic weakening, loosening, and osteolysis that can occur around implants.