Abstract
BackgroundSeptic arthritis is a serious joint disease often caused by Staphylococcus aureus (S. aureus). Receptor for Advanced Glycation End products (RAGE) has an important role in several infections. We sought to investigate the role of RAGE in staphylococcal septic arthritis and sepsis in mice.MethodsWild-type (WT) and RAGE deficient (RAGE-/-) mice were intra-articularly or intravenously inoculated with an arthritic or septic dose of S. aureus LS-1 strain. Clinical arthritis, weight development and mortality were monitored for 14 days. Serum levels of cytokines, kidney bacterial loads as well as micro-CT and histopathology of the joints were assessed.ResultsRAGE-/- mice with septic arthritis had significantly lower IL-17A and higher bone mineral density (BMD) compared to the control group. However, no significant differences between the groups were observed regarding the weight loss, the severity and frequency of arthritis, and bacterial loads in the kidneys. In mice with sepsis, the overall mortality rate was similar in RAGE-/- (39%) and in WT mice (45%). However, RAGE-/- mice with sepsis had significantly higher bacterial load in their kidneys compared to the WT controls. In line with data from hematogenous S. aureus arthritis, RAGE deficiency had no impact on arthritis severity in local joint infection.ConclusionsOur results indicate that lack of RAGE has no significant impact on septic arthritis. However, RAGE-/- mice had significantly higher BMD compared to WT mice, which coincided with lower IL-17A in RAGE-/- mice. In sepsis, RAGE deficiency impairs bacterial kidney clearance.
Highlights
Staphylococcus aureus (S. aureus) is a gram-positive bacterium that usually colonizes humans, mostly in the anterior nares and the skin
In line with data from hematogenous S. aureus arthritis, Receptor for Advanced Glycation End products (RAGE) deficiency had no impact on arthritis severity in local joint infection
Our results indicate that lack of RAGE has no significant impact on septic arthritis
Summary
Staphylococcus aureus (S. aureus) is a gram-positive bacterium that usually colonizes humans, mostly in the anterior nares and the skin. Septic arthritis is considered as one of the most aggressive joint diseases and S. aureus is the most prevalent cause of this severe disease. The joint damage caused by septic arthritis is often irreversible, even when immediate treatment is initiated [2]. For those who survive, more than half will have permanent joint dysfunction severely affecting their daily life [3]. The frequency of septic arthritis is 10 times higher in patients with pre-existing joint diseases [4]. Septic arthritis is a serious joint disease often caused by Staphylococcus aureus (S. aureus). We sought to investigate the role of RAGE in staphylococcal septic arthritis and sepsis in mice
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