Abstract
Septic arthritis, most often caused by Staphylococcus aureus, is a rapidly progressive and destructive joint disease with substantial mortality and morbidity. Staphylococcus aureus lipoproteins (Lpps) are known to induce arthritis and bone destruction. Here, we aimed to investigate the bone resorptive effect of S. aureus Lpps in a murine arthritis model by intra-articular injection of purified S. aureus Lpps, synthetic lipopeptides, and live S. aureus strains. Analyses of the bone mineral density (BMD) of the distal femur bone were performed. Intra-articular injection of both live S. aureus and purified S. aureus Lpps were shown to significantly decrease total- and trabecular BMD. Liquid chromatography–mass spectrometry analyses revealed that the Lpps expressed by S. aureus SA113 strain contain both diacyl and triacyl lipid moieties. Interestingly, synthetic diacylated lipopeptide, Pam2CSK4, was more potent in inducing bone resorption than synthetic triacylated lipopeptide, Pam3CSK4. Modified lipoproteins lacking the lipid moiety were deprived of their bone resorptive abilities. Monocyte depletion by clodronate liposomes fully abrogated the bone resorptive capacity of S. aureus lipoproteins. Our data suggest that S. aureus Lpps induce bone resorption in locally-induced murine arthritis, an effect mediated by their lipid-moiety through monocytes/macrophages.
Highlights
Septic arthritis remains one of the most dangerous joint diseases due to its rapidly progressive and destructive nature (Sharff et al, 2013)
To study the effects of S. aureus on bone mineral density (BMD) in mice with septic arthritis, NMRI mice were i.a. injected with either S. aureus LS-1 strain, a pathogenic S. aureus strain that was originally isolated from a mouse that spontaneously developed septic arthritis (Bremell et al, 1991), or with phosphate-buffered saline (PBS), and control NMRI mice were injected with PBS in both knees
Significant differences in totaland trabecular BMD were observed between the healthy mouse femoral bone and the femoral bone from PBS injected knee joints from the mice infected with S. aureus in their collateral knees (Figures 1C,D), suggesting that systemic inflammation caused by S. aureus local infection has significant impact on the bone metabolism
Summary
Septic arthritis remains one of the most dangerous joint diseases due to its rapidly progressive and destructive nature (Sharff et al, 2013). In a local murine knee joint model (Mohammad et al, 2019), the initiated innate immune response has a profound impact on the inflammation and destruction of joints. This effect is primarily mediated by the recruitment of monocytes/macrophages (Mohammad et al, 2019), which are the cells that can differentiate into osteoclasts and induce bone resorption (Boyle et al, 2003). Bacterial Lpps, ligands to TLRs, can affect the differentiation and activation of osteoclasts and osteoblasts Staphylococcus aureus produces both diacylated and triacylated Lpps depending on the environment (Kurokawa et al, 2009, 2012). We hypothesize that S. aureus Lpp is one of the driving forces for bone resorption in septic arthritis
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