Filifactor alocis‐derived extracellular vesicles inhibit osteogenesis through TLR2 signaling
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 vesicl...
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Veröffentlicht in: | Molecular oral microbiology 2020-10, Vol.35 (5), p.202-210 |
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description | 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. |
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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.</description><identifier>ISSN: 2041-1006</identifier><identifier>EISSN: 2041-1014</identifier><identifier>DOI: 10.1111/omi.12307</identifier><identifier>PMID: 33044804</identifier><language>eng</language><publisher>Denmark: Wiley Subscription Services, Inc</publisher><subject>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 ; 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</subject><ispartof>Molecular oral microbiology, 2020-10, Vol.35 (5), p.202-210</ispartof><rights>2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><rights>2020 John Wiley & Sons A/S</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3537-f714e8ca97ef2553afca95097d4a36fe3d8c5a338938f6bb674453d1aac1a5c93</citedby><cites>FETCH-LOGICAL-c3537-f714e8ca97ef2553afca95097d4a36fe3d8c5a338938f6bb674453d1aac1a5c93</cites><orcidid>0000-0002-2887-3909 ; 0000-0003-3743-7209</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fomi.12307$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fomi.12307$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33044804$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Song, Min‐Kyoung</creatorcontrib><creatorcontrib>Kim, Hyun Young</creatorcontrib><creatorcontrib>Choi, Bong‐Kyu</creatorcontrib><creatorcontrib>Kim, Hong‐Hee</creatorcontrib><title>Filifactor alocis‐derived extracellular vesicles inhibit osteogenesis through TLR2 signaling</title><title>Molecular oral microbiology</title><addtitle>Mol Oral Microbiol</addtitle><description>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.</description><subject>Alveolar bone</subject><subject>Animals</subject><subject>Biomarkers</subject><subject>Biomedical materials</subject><subject>BMSC</subject><subject>Bone loss</subject><subject>Bone turnover</subject><subject>Cell Differentiation</subject><subject>Clostridiales</subject><subject>Dentistry</subject><subject>Differentiation (biology)</subject><subject>extracellular vesicle</subject><subject>Extracellular Vesicles</subject><subject>Filifactor alocis</subject><subject>Gene expression</subject><subject>Gum disease</subject><subject>Immunostimulation</subject><subject>MAP kinase</subject><subject>Mesenchymal Stem Cells - cytology</subject><subject>Mesenchyme</subject><subject>Mice</subject><subject>Mineralization</subject><subject>Osteogenesis</subject><subject>Osteoprotegerin</subject><subject>Pathogenesis</subject><subject>Periodontitis</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Stromal cells</subject><subject>Teeth</subject><subject>TLR2 protein</subject><subject>Toll-Like Receptor 2 - metabolism</subject><subject>Toll-like receptors</subject><subject>TRANCE protein</subject><subject>Vesicles</subject><issn>2041-1006</issn><issn>2041-1014</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10M1KAzEUBeAgipbqwheQATe6aJtMkslkKcWfQkUQ3TqkmTttJJ3UZKbqzkfwGX0S01a7ELybXMLH4XIQOia4T-IM3Nz0SUqx2EGdFDPSI5iw3e2OswN0FMIzjkMJE0LsowNKMWM5Zh30dGWsqZRunE-UddqEr4_PErxZQpnAW-OVBmtbq3yyhGC0hZCYemYmpklcaMBNoY7_IWlm3rXTWfIwvk-TYKa1sqaeHqK9StkARz9vFz1eXT4Mb3rju-vR8GLc05RT0asEYZBrJQVUKedUVXHnWIqSKZpVQMtcc0VpLmleZZNJJhjjtCRKaaK4lrSLzja5C-9eWghNMTdhdbmqwbWhSBmTUnIp00hP_9Bn1_p47lplaSa4IFGdb5T2LgQPVbHwZq78e0Fwseq9iL0X696jPflJbCdzKLfyt-UIBhvwaiy8_59U3N2ONpHffZuNnw</recordid><startdate>202010</startdate><enddate>202010</enddate><creator>Song, Min‐Kyoung</creator><creator>Kim, Hyun Young</creator><creator>Choi, Bong‐Kyu</creator><creator>Kim, Hong‐Hee</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2887-3909</orcidid><orcidid>https://orcid.org/0000-0003-3743-7209</orcidid></search><sort><creationdate>202010</creationdate><title>Filifactor alocis‐derived extracellular vesicles inhibit osteogenesis through TLR2 signaling</title><author>Song, Min‐Kyoung ; Kim, Hyun Young ; Choi, Bong‐Kyu ; Kim, Hong‐Hee</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3537-f714e8ca97ef2553afca95097d4a36fe3d8c5a338938f6bb674453d1aac1a5c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Alveolar bone</topic><topic>Animals</topic><topic>Biomarkers</topic><topic>Biomedical materials</topic><topic>BMSC</topic><topic>Bone loss</topic><topic>Bone turnover</topic><topic>Cell Differentiation</topic><topic>Clostridiales</topic><topic>Dentistry</topic><topic>Differentiation (biology)</topic><topic>extracellular vesicle</topic><topic>Extracellular Vesicles</topic><topic>Filifactor alocis</topic><topic>Gene expression</topic><topic>Gum disease</topic><topic>Immunostimulation</topic><topic>MAP kinase</topic><topic>Mesenchymal Stem Cells - cytology</topic><topic>Mesenchyme</topic><topic>Mice</topic><topic>Mineralization</topic><topic>Osteogenesis</topic><topic>Osteoprotegerin</topic><topic>Pathogenesis</topic><topic>Periodontitis</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Stromal cells</topic><topic>Teeth</topic><topic>TLR2 protein</topic><topic>Toll-Like Receptor 2 - metabolism</topic><topic>Toll-like receptors</topic><topic>TRANCE protein</topic><topic>Vesicles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Song, Min‐Kyoung</creatorcontrib><creatorcontrib>Kim, Hyun Young</creatorcontrib><creatorcontrib>Choi, Bong‐Kyu</creatorcontrib><creatorcontrib>Kim, Hong‐Hee</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular oral microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Song, Min‐Kyoung</au><au>Kim, Hyun Young</au><au>Choi, Bong‐Kyu</au><au>Kim, Hong‐Hee</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Filifactor alocis‐derived extracellular vesicles inhibit osteogenesis through TLR2 signaling</atitle><jtitle>Molecular oral microbiology</jtitle><addtitle>Mol Oral Microbiol</addtitle><date>2020-10</date><risdate>2020</risdate><volume>35</volume><issue>5</issue><spage>202</spage><epage>210</epage><pages>202-210</pages><issn>2041-1006</issn><eissn>2041-1014</eissn><abstract>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.</abstract><cop>Denmark</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33044804</pmid><doi>10.1111/omi.12307</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-2887-3909</orcidid><orcidid>https://orcid.org/0000-0003-3743-7209</orcidid></addata></record> |
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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 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 |
title | Filifactor alocis‐derived extracellular vesicles inhibit osteogenesis through TLR2 signaling |
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