Extracellular vesicles derived from the periodontal pathogen Filifactor alocis induce systemic bone loss through Toll-like receptor 2


Posted: 2021-10-14 19:00:00
J Extracell Vesicles . 2021 Oct;10(12):e12157. doi: 10.1002/jev2.12157. Affiliations Expand Affiliations 1 Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, Republic of Korea. 2 Department of Cell and Developmental Biology, School of Dentistry, Seoul National University, Seoul, Republic of Korea. 3 Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. 4 Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. 5 Dental Research Institute, Seoul National University, Seoul, Republic of Korea. Item in Clipboard Hyun Young Kim et al. J Extracell Vesicles. 2021 Oct. Show details Display options Display options Format J Extracell Vesicles . 2021 Oct;10(12):e12157. doi: 10.1002/jev2.12157. Affiliations 1 Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, Republic of Korea. 2 Department of Cell and Developmental Biology, School of Dentistry, Seoul National University, Seoul, Republic of Korea. 3 Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. 4 Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. 5 Dental Research Institute, Seoul National University, Seoul, Republic of Korea. Item in Clipboard CiteDisplay options Display options Format Abstract Periodontitis is an inflammatory disease induced by local infection in tooth-supporting tissue. 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-derived 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 Filifactor alocis, a Gram-positive, anaerobic periodontal pathogen, in systemic bone loss and osteoclast differentiation. F. alocis EVs accumulated in the long bones of mice after intraperitoneal administration. These EVs induced proinflammatory cytokines, osteoclastogenesis, and bone resorption via Toll-like receptor 2 (TLR2). The phase separation of F. alocis EVs showed that amphiphilic molecules were responsible for the induced bone resorption and osteoclastogenesis. The osteoclastogenic effects of F. alocis EVs were reduced by lipoprotein lipase. Proteomic analysis of the amphiphilic molecules identified seven lipoproteins. Our results indicate that lipoprotein-like molecules in F. alocis EVs may contribute to systemic bone loss via TLR2. Keywords: TLR2; bacterial extracellular vesicles; bone resorption; lipoproteins; osteoclastogenesis. © 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles. References REFERENCES Armbruster, K. M., & Meredith, T. C. (2018). Enrichment of bacterial lipoproteins and preparation of N-terminal lipopeptides for structural determination by mass spectrometry. Journal of Visualized Experiments, 21(135), 56842. https://doi.org/10.3791/56842 Armstrong, C. L., Miralda, I., Neff, A. C., Tian, S., Vashishta, A., Perez, L., Le, J., Lamont, R. J., & Uriarte, S. M. (2016). Filifactor alocis promotes neutrophil degranulation and chemotactic activity. Infection and Immunity, 84(12), 3423-3433. https://doi.org/10.1128/IAI.00496-16 Aruni, A. W., Roy, F., & Fletcher, H. M. (2011). Filifactor alocis has virulence attributes that can enhance its persistence under oxidative stress conditions and mediate invasion of epithelial cells by Porphyromonas gingivalis. Infection and Immunity, 79(10), 3872-3886. https://doi.org/10.1128/Iai.05631-11 Aruni, W., Chioma, O., & Fletcher, H. M. (2014). Filifactor alocis: The newly discovered kid on the block with special talents. Journal of Dental Research, 93(8), 725-732. https://doi.org/10.1177/0022034514538283 Azuma, Y., Kaji, K., Katogi, R., Takeshita, S., & Kudo, A. (2000). Tumor necrosis factor-α induces differentiation of and bone resorption by osteoclasts. Journal of Biological Chemistry, 275(7), 4858-4864. https://doi.org/10.1074/jbc.275.7.4858 Show all 72 references Grant support [x] Cite Copy Format: Send To [x]

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