Οι μεταλλοπρωτεάσες και οι ενδογενείς αναστολείς τους από περιπροθετικούς ιστούς άσηπτα χαλαρωμένων προθέσεων αρθροπλαστικής

Abstract

In this study the biological mechanisms, which contribute to aseptic loosening process, were evaluated. Periprosthetic tissues (IFT and PCT) and liquids (PSSF) from five patients, who subjected to hip revision due to aseptic loosening, were collected. The possibility of septic loosening was, by histopathological and culture examinations, excluded. Extraction of tissues and dialysis were, in the presence of proteinases inhibitors, performed in order to exclude the in vitro activation of the sample-enzymes. Collagenolytic and gelatinolytic activity were, in all samples, detected. In order to examine the gelatinolytic activity, all samples were subjected in gelatin zymography and the lysis bands were evaluated. The collagenolytic activity was examined by using the DNP-S peptide and reverse phase high performance liquid chromatography (RP-HPLC). The activities, mentioned above, were the outcome of, expressed in periprosthetic tissues, MMPs. The gelatinolytic activity was the result of gelatinases (MMP-2 and MMP-9), which were mainly in complex with TIMPs forms detected. The specific gelatinolytic activities of the samples were almost equal, independently the type of arthroplasty and the presence or absence of osteolysis. In PSSF samples low activity was detected. Collagenolytic activity, which was higher in samples collected from osteolytic lesions, was the result of presence and action of interstitial callagenases. MMP-13 seems to have the major contribution, compared to MMP-1 in collagenolytic activity. MT1-MMP was not detected, possibly due to the extraction methods. In more recent and unpublished results, MT1-MMP was detected in complex to TIMP-2. In brief, different members of the MMP family are expressed in periprosthetic tissues and fluids. These MMPs contribute in different way in loosening and osteolysis processes. The fact that in PCTs high activities were measured can support the hypothesis that all the biological events that lead to loosening start to take place in the PCT tissue. The contribution of each MMP in these processes has to be elucidated in order to try to decelerate them by using selective MMPs-inhibitors. In order to evaluate the possible usage of several well-known non-steroidal anti-inflammatory drugs for retarding the loosening process, the in vitro effect of these drugs in the IFT- induced production of MMPs and TIMPs was studied. Because of the complexity of the involved in pathogenesis factors, the effect of the drugs in other soluble cytokines (such as IL-6, IL-1β, TNF-a) and PGE2 was also measured. For all these experiments cultures of IFT of ten patients were used. Aceclofenac, Piroxicam, Tenoxicam and Indomethacin were used. The drugs didn’t have a statistically significant effect in the MMPs or TIMPs production. In all cases the inhibitory effect on PGE2 was potent. Aceclofnac and tenoxicam reduced strongly the IL-6 and TNF-α levels. Finally the drugs seemed to induce the ΙL-1β levels (especially aceclofenac). More experimental studies are necessary for supporting the usage of the tested drugs, for retarding the aseptic loosening phenomenon. In vivo studies will also be useful.