Lipoproteins Cause Bone Resorption in a Mouse Model of Septic Arthritis.

Septic arthritis, most often caused by , is a rapidly progressive and destructive joint disease with substantial mortality and morbidity. lipoproteins (Lpps) are known to induce arthritis and bone destruction. Here, we aimed to investigate the bone resorptive effect of Lpps in a murine arthritis model by intra-articular injection of purified Lpps, synthetic lipopeptides, and live strains. Analyses of the bone mineral density (BMD) of the distal femur bone were performed. Intra-articular injection of both live and purified Lpps were shown to significantly decrease total- and trabecular BMD. Liquid chromatography-mass spectrometry analyses revealed that the Lpps expressed by SA113 strain contain both diacyl and triacyl lipid moieties. Interestingly, synthetic diacylated lipopeptide, PamCSK, was more potent in inducing bone resorption than synthetic triacylated lipopeptide, PamCSK. 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 lipoproteins. Our data suggest that Lpps induce bone resorption in locally-induced murine arthritis, an effect mediated by their lipid-moiety through monocytes/macrophages.