Filifactor alocis‐derived extracellular vesicles inhibit osteogenesis through TLR2 signaling

• Published in: Molecular oral microbiology Vol. 35; no. 5; pp. 202 - 210
• Main Authors: Song, Min‐Kyoung, Kim, Hyun Young, Choi, Bong‐Kyu, Kim, Hong‐Hee
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.10.2020
• Subjects: Alveolar bone; Animals; Biomarkers; Biomedical materials; BMSC; Bone loss; Bone turnover; Cell Differentiation; Clostridiales; Dentistry; Differentiation (biology); extracellular vesicle; Extracellular Vesicles; Filifactor alocis; Gene expression; Gum disease; Immunostimulation; MAP kinase; Mesenchymal Stem Cells - cytology; Mesenchyme; Metabolism; Mice; Mineralization; Osteogenesis; Osteoprotegerin; Pathogenesis; Periodontitis; Signal Transduction; Signaling; Stromal cells; Teeth; TLR2 protein; Toll-Like Receptor 2 - metabolism; Toll-like receptors; TRANCE protein; Vesicles; Filifactor alocis; osteogenesis; BMSC; extracellular vesicle; periodontitis
• ISSN: 2041-1006; 2041-1014
• DOI: 10.1111/omi.12307

Filifactor alocis, an asaccharolytic anaerobic Gram‐positive rod (AAGPR), is an emerging marker of periodontitis. Severe periodontitis causes destruction of the alveolar bone that supports teeth and can even lead to tooth loss. Based on our previous report that F. alocis‐derived extracellular vesicles (FA EVs) contain various effector molecules and have immunostimulatory activity, we investigated the effect of FA EVs on osteogenesis using mouse bone‐derived mesenchymal stromal cells (BMSCs). FA EVs dramatically inhibited bone mineralization similar to whole bacteria and reduced the expression levels of osteogenic marker genes. The osteogenic differentiation of TLR2‐deficient BMSCs was not inhibited by FA EVs, suggesting that their inhibitory effect on osteogenesis is dependent on TLR2 signaling. FA EVs effectively activated TLR2 downstream signaling of the MAPK and NF‐κB pathways. In addition, FA EVs regulated RANKL and OPG gene expression, increasing the RANKL/OPG ratio in BMSCs in a TLR2‐dependent manner. Our study suggests that F. alocis‐derived EVs interfere with bone metabolism via TLR2 activation, providing insight into the pathogenesis of bone loss associated with periodontitis. Filifactor alocis‐derived extracellular vesicles (FA EVs) inhibit osteogenic differentiation of bone‐derived mesenchymal stromal cells (BMSCs) in a TLR2‐dependent manner and regulate the expression of RANKL/OPG, which promotes osteoclastogenesis.