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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, Pam 2 CSK 4 , was more potent in inducing bone resorption than synthetic triacylated lipopeptide, Pam 3 CSK 4 . 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.

Lipoproteins Cause Bone Resorption in a Mouse Model of Staphylococcus aureus Septic Arthritis