Receptor activator of nuclear factor kappaB ligand is expressed in resident and inflammatory cells in aseptic and septic prosthesis loosening. Scand J Rheumatol 2003;32(5):287-94
Date
12/24/2003Pubmed ID
14690142DOI
10.1080/03009740310003929Scopus ID
2-s2.0-0344010230 (requires institutional sign-in at Scopus site) 53 CitationsAbstract
OBJECTIVE: The pathogenesis of periprosthetic bone loss in aseptic and septic prosthesis loosening is unclear. There is considerable evidence that macrophages and osteoclasts play a key role in focal bone erosion and osteolysis around the prosthesis. RANKL (receptor activator of nuclear factor kappaB ligand) was shown to be a potent osteoclastogenic factor, and to be involved in bone destruction of myeloma and rheumatoid arthritis patients. Osteoprotegerin (OPG) is the natural RANKL inhibitor and may prevent periprosthetic bone loss.
METHODS: The presence and distribution of RANKL, its receptor RANK and OPG in the periprosthetic interface of septically (n = 5) and aseptically (n = 6) loosened prostheses was examined by immunohistochemistry and immunoblotting. Additionally, the immunophenotype of the inflammatory infiltrate was determined [CD3, CD68, Ki-67, tartrate-resistant acid posphatase (TRAP)].
RESULTS: Aseptic and septic cases revealed a different histopathologic pattern. However, in all cases RANKL and RANK could be demonstrated in macrophages and giant cells. In addition, RANKL detected by immunoblot analysis proved to have the same molecular weight as a recombinant RANKL used as a control (31 kD and approximately 48 kD). OPG was detected in aseptic loosening, where macrophages showed a strong staining, but multinucleated giant cells were only weakly stained. A weak OPG staining was also observed in septic loosening.
CONCLUSION: The pathogenesis of bone loss in septic loosening remains unclear, because the septic membrane bears few macrophages and giant cells, and half of them express OPG. In aseptic loosening, macrophages might not be stimulated by RANKL as a result of OPG expression. But multinucleated giant cells may be activated, as they hardly express OPG. They might be responsible for periprosthetic bone loss in aseptic loosening as a result of their RANKL and RANK expression.
Author List
Gehrke T, Sers C, Morawietz L, Fernahl G, Neidel J, Frommelt L, Krenn VMESH terms used to index this publication - Major topics in bold
AgedAged, 80 and over
Arthroplasty, Replacement, Hip
Arthroplasty, Replacement, Knee
Blotting, Western
Carrier Proteins
Female
Giant Cells
Glycoproteins
Hip Prosthesis
Humans
Immunohistochemistry
Knee Prosthesis
Macrophages
Male
Membrane Glycoproteins
Middle Aged
Osteolysis
Osteoprotegerin
Prosthesis Failure
Prosthesis-Related Infections
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B
Receptors, Cytoplasmic and Nuclear
Receptors, Tumor Necrosis Factor
