AUTHOR=Schultz Michelle , Mohammad Majd , Nguyen Minh-Thu , Hu Zhicheng , Jarneborn Anders , Wienken Carina M. , Froning Matti , Pullerits Rille , Ali Abukar , Hayen Heiko , Götz Friedrich , Jin Tao 

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

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.843799

DOI=10.3389/fmicb.2022.843799

ISSN=1664-302X

ABSTRACT=<p>Septic arthritis, most often caused by <italic>Staphylococcus aureus</italic>, is a rapidly progressive and destructive joint disease with substantial mortality and morbidity. <italic>Staphylococcus aureus</italic> lipoproteins (Lpps) are known to induce arthritis and bone destruction. Here, we aimed to investigate the bone resorptive effect of <italic>S. aureus</italic> Lpps in a murine arthritis model by intra-articular injection of purified <italic>S. aureus</italic> Lpps, synthetic lipopeptides, and live <italic>S. aureus</italic> strains. Analyses of the bone mineral density (BMD) of the distal femur bone were performed. Intra-articular injection of both live <italic>S. aureus</italic> and purified <italic>S. aureus</italic> Lpps were shown to significantly decrease total- and trabecular BMD. Liquid chromatography–mass spectrometry analyses revealed that the Lpps expressed by <italic>S. aureus</italic> SA113 strain contain both diacyl and triacyl lipid moieties. Interestingly, synthetic diacylated lipopeptide, Pam<sub>2</sub>CSK<sub>4</sub>, was more potent in inducing bone resorption than synthetic triacylated lipopeptide, Pam<sub>3</sub>CSK<sub>4</sub>. 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 <italic>S. aureus</italic> lipoproteins. Our data suggest that <italic>S. aureus</italic> Lpps induce bone resorption in locally-induced murine arthritis, an effect mediated by their lipid-moiety through monocytes/macrophages.</p>