Expression of caspase-8 and caspase-3 proteins in interface membranes from aseptically loose total hip arthroplasty

Abstract

The terminal events leading to periprosthetic osteolysis are multifactorial and modulation of this process after the stage of mediator release has been demonstrated futile. We demonstrated that ceramic induce macrophage apoptosis in vitro. More recently, we and others demonstrated the presence of apoptosis in interface membranes (IMs) from aseptically loose total hip arthroplasty (THA). The purpose of this study was to characterize the mechanisms leading to apoptosis in these pseudomembranes. Western blot analysis was used to characterize the expression of caspase-3, caspase-8, poly(ADP-ribose)polymerase (PARP), and p53 proteins in IM from 35 patients (40 specimens) with a mean age of 58 years (range, 28-88 years) at the time of revision. Tissue harvested at the time of routine hardware removal served as control. Our results show that caspase-3 and caspase-8 pro-enzymes were expressed in both control and IM tissues. Our results also showed that caspase-3 active fragment (17 kDa) as well as caspase-8 active fragment (18 kDa) were expressed in IMs but absent in control tissues. We also demonstrated that both the native PARP (113 kDa) and its proteolytic fragment (89 kDa) were present in osteolytic IMs. Control membranes expressed only the 113 kDa native form of PARP. The over-expression of caspase-3 caspase-8 active fragments and the presence of PARP fragment were observed on both the acetabular and femoral sides of the prostheses. Finally, our results showed the absence of p53 expression in both osteolytic IMs and control tissues. In conclusion, our results suggest that the caspase/PARP pathway plays an active role in the activity of IMs from aseptically loose THAs.