Matrix metalloproteinases and tissue inhibitors of metalloproteinases in joint fluid of the patients with loose artificial hip joints

The pseudojoint cavity formed in patients undergoing total hip arthroplasty (THA) is later remodeled to synovial membrane-like tissue, which produces pseudosynovial fluid. This pseudosynovium also is an important source of ma trix metalloproteinases (MMPs). As it is widely speculated that synovial fl uid MMPs may contribute to local tissue degradation in rheumatoid arthritis (RA) and osteoarthritis (OA), we hypothesize that locally produced MMPs ar e found in the pseudosynovial fluid, via which they have access to the impl ant-host interface, and that if they retain their proteolytic potential, th ey might contribute to aseptic loosening. Enzyme-linked immunosorbent assay (ELISA), immunoblotting, and zymography were used to analyze MMPs and tiss ue inhibitors of metalloproteinases (TIMPs) in synovial fluid in aseptic lo osening, which was compared to RA and OA. Pseudosynovial THA fluid was char acterized using low levels of MMP-1 but moderate levels of MMP-13 and MT1-M MP (MMP-14). Due to the lack of an appropriate assay, MMP-13 and MT1-MMP we re not similarly assessed, but the immunoblotting indicated that they were in the 56 kD intermediate proteolytically processed forms. The MMP-9 level was intermediate between RA and OA. MMP-2 was on a significant level, but t here were no differences among study groups. The THA group also was charact erized using relatively high levels of TIMP-1 and TIMP-2. Accordingly, MMP- 9 and MMP-2 were found to occur in the 92 kD and 72 kD proenzyme form, resp ectively, with full activity retained in all study groups. The data suggest that proMMP-2-TIMP-2 and proMMP-9-TIMP-1 complexes are formed in the pseud osynovial fluid due to the excess of TIMPs over MMPs in aseptic loosening o f THA. TIMP-complexed MMPs are resistant to MMP-mediated proteolytic activa tion, which may explain their latency and proenzyme zymogen form. Thus, for mation of stabilizing proMMP-TIMP complexes enable transportation of proMMP s far from their original site of production. Due to motion-associated cycl ic changes of the intra-articular pressure, fluid-phase MMPs stabilized by TIMPs might be absorbed to implant surfaces and interface tissues and help to dissect the implant/cement-to-bone interface in situ. Consequently, they may contribute to local proteolytic/tissue destructive events and aseptic loosening. (C) 1999 John Wiley & Sons, Inc.