Effects of extracellular vesicles derived from oral bacteria on osteoclast differentiation and activation

• Published in: Scientific reports Vol. 12; no. 1; p. 14239
• Main Authors: Kim, Hyun Young, Song, Min-Kyoung, Lim, Younggap, Jang, Ji Sun, An, Sun-Jin, Kim, Hong-Hee, Choi, Bong-Kyu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.08.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/262/2106; 631/250/808; 631/326/421; Alveolar bone; Bacteria; Bacterial vesicles; Bone loss; Cytokines; Dysbacteriosis; Extracellular vesicles; Humanities and Social Sciences; Immunostimulation; Lipase; Lipopolysaccharides; Lipoprotein lipase; Lipoproteins; Microbiota; Microorganisms; multidisciplinary; Osteoclastogenesis; Osteoprogenitor cells; Pathogens; Periodontitis; Polymyxin B; Probiotics; Science; Science (multidisciplinary); TLR2 protein; TLR4 protein; TLR9 protein; Toll-like receptors; Ultracentrifugation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-18412-4

Dysbiosis of the oral microbiota plays an important role in the progression of periodontitis, which is characterized by chronic inflammation and alveolar bone loss, and associated with systemic diseases. Bacterial extracellular vesicles (EVs) contain various bioactive molecules and show diverse effects on host environments depending on the bacterial species. Recently, we reported that EVs derived from Filifactor alocis, a Gram-positive periodontal pathogen, had osteoclastogenic activity. In the present study, we analysed the osteoclastogenic potency and immunostimulatory activity of EVs derived from the Gram-negative periodontal pathogens Porphyromonas gingivalis and Tannerella forsythia , the oral commensal bacterium Streptococcus oralis , and the gut probiotic strain Lactobacillus reuteri . Bacterial EVs were purified by density gradient ultracentrifugation using OptiPrep (iodixanol) reagent. EVs from P. gingivalis , T. forsythia , and S. oralis increased osteoclast differentiation and osteoclstogenic cytokine expression in osteoclast precursors, whereas EVs from L. reuteri did not. EVs from P. gingivalis , T. forsythia , and S. oralis preferentially activated Toll-like receptor 2 (TLR2) rather than TLR4 or TLR9, and induced osteoclastogenesis mainly through TLR2. The osteoclastogenic effects of EVs from P. gingivalis and T. forsythia were reduced by both lipoprotein lipase and polymyxin B, an inhibitor of lipopolysaccharide (LPS), while the osteoclastogenic effects of EVs from S. oralis were reduced by lipoprotein lipase alone. These results demonstrate that EVs from periodontal pathogens and oral commensal have osteoclastogenic activity through TLR2 activation by lipoproteins and/or LPS.