title: Extrinsic and intrinsic pathways of apoptosis in aseptic loosening after total hip replacement.
abstract: Particle-induced osteolysis is a major cause of aseptic loosening after total joint replacement. The purpose of the current study was to identify various apoptosis-related pathways in the cellular response to wear debris. Fas receptor, BAK and caspase-3 cleaved were evaluated immunohistochemically in capsules and interface membranes from patients with aseptic hip implant loosening. Moreover, we investigated local cellular proliferation, documented by the presence of Ki-67, to evaluate the proportion of apoptosis in relation to the proliferation in the different cells. We detected a strong expression of caspase-3 cleaved, Fas and BAK in macrophages, giant cells and T-lymphocytes. The fibroblasts showed caspase-3 cleaved and BAK, but no Fas staining. Demonstrated by Ki-67 staining, we found increased proliferation of macrophages and fibroblasts. Statistical analysis showed a significant positive correlation (p<0.001) between the above mentioned results and the presence of wear debris. The intensity of apoptosis and proliferation differed, depending on the extent of osteolysis. Overall, four different patterns of immunoreactivity were identified. We think, however, that in particle-induced osteolysis apoptosis is pathologically increased - a phenomenon also seen in other diseases. In these instances, the number and degree of apoptotic reactions are so great that the resulting cell remains cannot be completely removed. This leads to an increased excretion of fibrogenic mediators that could be responsible for increased proliferation of fibroblasts in spite of the increased apoptosis. Moreover, it leads to an increased excretion of cytokines which could be responsible for the activation of osteoclasts.
authors.affiliation: Department of Orthopaedics, University of Duisburg-Essen, Pattbergstrasse 1-3, 45239 Essen, Germany. stlandy@t-online.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Landgraeber
authors.forename: Marius
authors.initials: M
authors.lastname: von Knoch
authors.forename: Franz
authors.initials: F
authors.lastname: Löer
authors.forename: Alexander
authors.initials: A
authors.lastname: Wegner
authors.forename: Michael
authors.initials: M
authors.lastname: Tsokos
authors.forename: Björn
authors.initials: B
authors.lastname: Hussmann
authors.forename: Martin
authors.initials: M
authors.lastname: Totsch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D053148:Caspase 3 / Q000032:analysis; D049109:Cell Proliferation; D005260:Female; D006622:Hip Prosthesis / Q000009:adverse effects*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010014:Osteolysis / Q000209:etiology*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000032:analysis; D019014:fas Receptor / Q000032:analysis
chemical_list: C494772:BAK1 protein, human; D019394:Ki-67 Antigen; D050998:bcl-2 Homologous Antagonist-Killer Protein; D019014:fas Receptor; D053148:Caspase 3