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Periodontitis is associated with systemic bone diseases, but little is known about the mechanism of the causal effect of periodontitis on systemic bone resorption. Bacteria\u2010derived extracellular vesicles (EVs) act as natural carriers of virulence factors that are responsible for systemic inflammation. In this study, we investigated the role of EVs derived from <jats:italic>Filifactor alocis<\/jats:italic>, a Gram\u2010positive, anaerobic periodontal pathogen, in systemic bone loss and osteoclast differentiation. <jats:italic>F. alocis<\/jats:italic> EVs accumulated in the long bones of mice after intraperitoneal administration. These EVs induced proinflammatory cytokines, osteoclastogenesis, and bone resorption via Toll\u2010like receptor 2 (TLR2). The phase separation of <jats:italic>F. alocis<\/jats:italic> EVs showed that amphiphilic molecules were responsible for the induced bone resorption and osteoclastogenesis. The osteoclastogenic effects of <jats:italic>F. alocis<\/jats:italic> EVs were reduced by lipoprotein lipase. Proteomic analysis of the amphiphilic molecules identified seven lipoproteins. Our results indicate that lipoprotein\u2010like molecules in <jats:italic>F. alocis<\/jats:italic> EVs may contribute to systemic bone loss via TLR2.<\/jats:p>","DOI":"10.1002\/jev2.12157","type":"journal-article","created":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T12:47:55Z","timestamp":1634647675000},"source":"Crossref","is-referenced-by-count":86,"title":["Extracellular vesicles derived from the periodontal pathogen <i>Filifactor alocis<\/i> induce systemic bone loss through Toll\u2010like receptor 2"],"prefix":"10.1002","volume":"10","author":[{"given":"Hyun Young","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Oral Microbiology and Immunology School of Dentistry, Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min\u2010Kyoung","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology School of Dentistry, Seoul National University  Seoul Republic of Korea"},{"name":"Department of Internal Medicine Seoul National University Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Song","family":"Gho","sequence":"additional","affiliation":[{"name":"Department of Life Sciences Pohang University of Science and Technology (POSTECH)  Pohang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology School of Dentistry, Seoul National University  Seoul Republic of Korea"},{"name":"Dental Research Institute Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3743-7209","authenticated-orcid":false,"given":"Bong\u2010Kyu","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Oral Microbiology and Immunology School of Dentistry, Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,14]]},"reference":[{"issue":"135","key":"e_1_2_8_2_1","first-page":"56842","article-title":"Enrichment of bacterial lipoproteins and preparation of N\u2010terminal lipopeptides for structural determination by mass spectrometry","volume":"21","author":"Armbruster K. 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