Total Hip Arthroplasty Matrix Metalloproteinase TIMP ANALYSIS OF MEMBRANE TYPE 1 - MATRIX METALLOPROTEINASE, MATRIX METALLOPROTEINASE-2 AND TISSUE INHIBITOR OF METALLOPROTEINSE-2 IN LOOSE HIP PERIPROSTHETIC CONNECTIVE TISSUES

Introduction: The biocompatibility of total hip prostheses has been the subject of debate for three decades, and currently it appears evident that the loosening of technically well inserted prostheses is in part due to cellular responses in periprosthetic connective tissues. Despite of intensive research, the precise biological mechanisms responsible for the loosening of total hip joints have not been completely clarified yet. Extracellular matrix degradation and connective tissue remodeling around implants has been considered as major biological event in the loosening, and the contribution of matrix metalloproteinases (MMPs) and their inhibitors of MMPs as important (1, 2, 3, 4, 5). Although extensive localization of MMP-2 in loose hip joints have been reported, the role of MMP-2 has not been clarified because the activation system of proMMP-2 has been unknown (5). Recent research demonstrated that proMMP-2 is activated by membrane type-1 metalloproteinases (MT1MMP) (6) and is an important component of the ternary MT1-MMP/MMP2/tissue inhibitor of metalloproteinase-2 (TIMP-2) complex involved in the extracellular matrix remodeling (7). This study focused on the investigation of MT1-MMP combined with MMP-2 and TIMP-2 to clarify its regulatory dynamic at the protein-mRNA expression level in the cascade of extracellular connective tissue remodeling in relation to periprosthetic weakening of loose hip joints.