Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Landgraeber, S; Jaeckel, S; Löer, F; Wedemeyer, C; Hilken, G; Canbay, A; Totsch, M; von Knoch, M.
Pan-caspase inhibition suppresses polyethylene particle-induced osteolysis.
Apoptosis. 2009; 14(2):173-181
Doi: 10.1007/s10495-008-0297-3
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Tötsch Martin
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- Abstract:
- Particle-induced osteolysis is a major cause of aseptic loosening after total joint replacement. Earlier studies demonstrated apoptotic macrophages, giant cells, fibroblasts and T-lymphocytes in capsules and interface membranes of patients with aseptic hip implant loosening. The aim of the current study was to determine in a murine calvarial model of wear particle-induced osteolysis whether inhibition of apoptosis using the pan-caspase inhibitor BOC-D-FMK reduces aseptic loosening. Healthy 12-week-old male C57BL/6J mice were treated with UHMWPE particles and received a daily peritoneal injection of BOK-D-FMK, respectively only buffer at a dose of 3 mg/kg of body weight for 12 days until sacrifice. Bone resorption was measured by histomorphometry, micro CT (computed tomography) and TRAP-5b serum analysis. Apoptosis was measured using caspase-3 cleaved staining. The results demonstrated that UHMWPE particles induced stronger apoptotic reactions in macrophages and osteoblasts and increased bone resorption in non-specifically treated mice, whereas peritoneal application of BOC-D-FMK significantly counteracted these adverse particle-related effects. We think that in particle-induced osteolysis apoptosis is pathologically increased, and that failure to reduce the quantity of apoptotic bodies leads to an up-regulation of proinflammatory cytokines, which may be responsible for the induction of osteolysis. We showed for the first time in vivo that a reduction in apoptosis leads to a significant reduction in particle-induced osteolysis. Clinically, the apoptotic cascade could become an interesting novel therapeutic target to modulate particle-induced osteolysis.
- Find related publications in this database (using NLM MeSH Indexing)
- Acid Phosphatase - blood
- Animals -
- Benzyl Compounds - pharmacology
- Caspase 3 - metabolism
- Caspases - antagonists and inhibitors
- Hydrocarbons, Fluorinated - pharmacology
- Immunohistochemistry -
- Isoenzymes - blood
- Male -
- Mice -
- Mice, Inbred C57BL -
- Organ Size -
- Osteoclasts - drug effects Osteoclasts - pathology
- Osteolysis - blood Osteolysis - chemically induced Osteolysis - enzymology Osteolysis - prevention and control
- Polyethylenes -
- Prosthesis Implantation -
- Skull - drug effects Skull - enzymology Skull - pathology Skull - radiography
- X-Ray Microtomography -
- Find related publications in this database (Keywords)
- Apoptosis
- Wear debris
- Endoprosthesis
- Osteolysis