Vinsamlegast notið þetta auðkenni þegar þið vitnið til verksins eða tengið í það: http://hdl.handle.net/1946/18315
Background: Staphylococcus aureus septic arthritis can cause rapid joint destruction and osteoporosis. S. aureus-induced permanent joint damage and subsequent disability affects many patients, despite antibiotic treatment. Osteoclasts are the cells responsible for bone loss and joint destruction. These cells can be activated by inflammatory cytokine responses against infections. Recognition of pathogen-associated molecular patterns (PAMPs) via Toll-like receptors (TLR) is important for this cytokine-induction. Among the cytokines important for differentiation and activation of osteoclasts is the receptor activator of nuclear factor-κB ligand (RANKL). However, the role of RANKL in S. aureus-induced joint damage is not fully known. In this study we established an immunohistochemical method for quantification of RANKL expression in mouse bone and joint tissues allowing studies of the role of RANKL and TLR 2 signaling in S. aureus -induced bone loss.
Method: Two models of experimental inflammation were used. C57BL/6 mice were either inoculated intravenously with S. aureus to induce septic arthritis or subcutaneously injected over the skull bone with TLR-2 ligands.
Results: A specific immunohistochemical RANKL staining method was established. S. aureus septic arthritis significantly increased the local expression of RANKL in bone marrow, a finding that was accompanied with a significant loss of trabecular bone mineral density (BMD) and histopathological joint inflammation and destruction. Preliminary data showed no significant change of RANKL expression through TLR-2 activation in calvarial bone marrow. However, we observed a trend towards increased RANKL expression in periosteal inflammatory infiltrates in TLR2 ligand-stimulated calvarias a finding that needs to be further evaluated.
Conclusions: Since the local expression of RANKL is upregulated in S.aureus-induced arthritis anti-RANKL targeted therapy might prove beneficial against local bone destruction and joint destruction. Furthermore, preliminary results indicate that S. aureus-induced bone loss is not mediated via TLR-2 mediated RANKL induction. Thus, recognition of S. aureus bacteria via other mechanisms than TLR-2 signaling might play a role for the RANKL induction and bone destruction.
Key words: RANKL; osteoclasts; TLR-2; bone loss; S.aureus; mice.
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