Over-expression of P53/Bak in Aseptic Loosening After Total Hip Replacement.
From: Department of Orthopaedics, University of Duisburg-Essen, Pattbergstrasse 1-3, 45239 Essen, Germany. stlandy@arcor.de
Biomaterials
- Publish Date: May 2006
- ISSN: 0142-9612
- Volume: 27
- Issue: 15
- Pages: 3010-20
- Medium: Print
- Language: English
- Citation (JAMA): Landgraeber Stefan, Toetsch Martin, Wedemeyer Christian, et al. Over-expression of P53/Bak in Aseptic Loosening After Total Hip Replacement.. Biomaterials May 2006;27:3010-20
Abstract
Particle-induced osteolysis is a major cause of aseptic loosening after total joint replacement. The possible induction of apoptosis has not been addressed in great detail. Thus far, it has been shown that ceramic and polyethylene particles can induce apoptosis of macrophages in vitro. The purpose of this study was to test the hypothesis that wears debris generated from total hip arthroplasty could induce cellular damage and apoptosis in vivo. We therefore determined by immunohistochemical methods if increased expression of p53, an important transcription factor, and BAK and Bcl-2, two important regulators of apoptosis, can be found in interface membranes and capsules of hips with aseptically loose implants. Strongly positive immunohistochemical staining for p53 and BAK was found in peri-implant tissues from patients with aseptic hip implant loosening. Differentiation of various cell types showed that macrophages stained positive for p53 in all capsule and interface specimens. p53 was frequently detected in giant cells. Positive staining of BAK in macrophages and giant cells was seen in all specimens. Some positive reactions were observed in fibroblasts, only two of 19 cases stained for p53 and three cases for BAK within synovial cells. Positive macrophages and giant cells were localized around polyethylene particles. While T-lymphocytes showed a regular BAK-staining, the other leukocytes were negative. Statistical analyses showed significant positive correlations (p < 0.001) between the presence of polyethylene and metal debris and the expression of BAK and p53. Polyethylene particles were surrounded by more positive macrophages and giant cells than were metal particles, indicating that polyethylene debris may be a stronger inductor of cell cycle arrest and apoptosis than metal debris. In this study apoptosis of macrophages, giant cells and T-lymphocytes in capsules and interface membranes of patients with aseptic hip implant loosening has been demonstrated in vivo. It is possible that the apoptotic cascade could evolve as a novel therapeutic target to prevent particle-induced osteolysis.
Mesh Headings (Keywords): Adult, Aged, Arthroplasty, Replacement, Hip, Cells, Cultured, Female, Foreign-Body Reaction, Hip Joint, Humans, Joint Instability, Macrophages, Male, Middle Aged, Prosthesis-Related Infections, Tumor Suppressor Protein p53, bcl-2 Homologous Antagonist-Killer Protein
Check for Full Text / PubMed Unique Identifier (PMID): 16445975
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.