Osteoprotegerin protects endothelial cells against apoptotic cell death induced by Porphyromonas gingivalis cysteine proteinases
Abstract Osteoprotegerin (OPG) is a key regulator of osteoclastogenesis during the progression of periodontitis. Recent reports suggest that osteoprotegerin may also prevent arterial calcification and contribute to endothelial cell survival. To determine whether the vascular functions of osteoproteg...
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| Veröffentlicht in: | FEMS microbiology letters 2006-11, Vol.264 (2), p.238-245 |
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| creator | Kobayashi-Sakamoto, Michiyo Hirose, Kimiharu Nishikata, Makoto Isogai, Emiko Chiba, Itsuo |
| description | Abstract
Osteoprotegerin (OPG) is a key regulator of osteoclastogenesis during the progression of periodontitis. Recent reports suggest that osteoprotegerin may also prevent arterial calcification and contribute to endothelial cell survival. To determine whether the vascular functions of osteoprotegerin are involved in periodontitis, we examined whether osteoprotegerin contributed to the survival of endothelial cells damaged by Porphyromonas gingivalis cysteine proteinases (gingipains). Gingipain proteinases cleave a broad range of host proteins, and are important virulence factors of P. gingivalis, a major causative bacterium of adult periodontitis. Human microvascular endothelial cells (HMVEC) were exposed to activated gingipain extracts from P. gingivalis 381, with and without pretreatment with osteoprotegerin. Cell viability was quantified by the tetrazolium (WST-8) reduction assay, and apoptosis was examined using Hoechst 33342 nuclear staining. After 16 h of treatment with activated gingipain extracts, HMVEC showed near-complete detachment from the tissue culture dish, and apoptosis was evident by 24 h. Pretreatment of HMVEC with osteoprotegerin reduced the extent of both cellular detachment and apoptotic cell death. Our results indicated that osteoprotegerin pretreatment protected HMVEC against detachment and apoptotic cell death induced by gingipain-active bacterial cell extracts. These results also suggest that osteoprotegerin may function as a survival factor for endothelial cells during periodontitis. |
| doi_str_mv | 10.1111/j.1574-6968.2006.00458.x |
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Osteoprotegerin (OPG) is a key regulator of osteoclastogenesis during the progression of periodontitis. Recent reports suggest that osteoprotegerin may also prevent arterial calcification and contribute to endothelial cell survival. To determine whether the vascular functions of osteoprotegerin are involved in periodontitis, we examined whether osteoprotegerin contributed to the survival of endothelial cells damaged by Porphyromonas gingivalis cysteine proteinases (gingipains). Gingipain proteinases cleave a broad range of host proteins, and are important virulence factors of P. gingivalis, a major causative bacterium of adult periodontitis. Human microvascular endothelial cells (HMVEC) were exposed to activated gingipain extracts from P. gingivalis 381, with and without pretreatment with osteoprotegerin. Cell viability was quantified by the tetrazolium (WST-8) reduction assay, and apoptosis was examined using Hoechst 33342 nuclear staining. After 16 h of treatment with activated gingipain extracts, HMVEC showed near-complete detachment from the tissue culture dish, and apoptosis was evident by 24 h. Pretreatment of HMVEC with osteoprotegerin reduced the extent of both cellular detachment and apoptotic cell death. Our results indicated that osteoprotegerin pretreatment protected HMVEC against detachment and apoptotic cell death induced by gingipain-active bacterial cell extracts. These results also suggest that osteoprotegerin may function as a survival factor for endothelial cells during periodontitis.</description><identifier>ISSN: 0378-1097</identifier><identifier>EISSN: 1574-6968</identifier><identifier>DOI: 10.1111/j.1574-6968.2006.00458.x</identifier><identifier>PMID: 16981905</identifier><identifier>CODEN: FMLED7</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Apoptosis ; Apoptosis - drug effects ; Apoptosis - physiology ; Arteriosclerosis ; Bacteriology ; Biological and medical sciences ; Biomedical materials ; Calcification ; Calcification (ectopic) ; Cell culture ; Cell death ; Cell survival ; Cell viability ; Cysteine ; Cysteine Endopeptidases - pharmacology ; Endothelial cells ; Endothelial Cells - cytology ; Endothelial Cells - drug effects ; Endothelium, Vascular - cytology ; Endothelium, Vascular - drug effects ; Fundamental and applied biological sciences. Psychology ; Gingipain ; gingipains ; Humans ; Microbiology ; Microvasculature ; Mortality ; Osteoclastogenesis ; Osteoprotegerin ; Osteoprotegerin - metabolism ; Osteoprotegerin - pharmacology ; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains ; Periodontitis ; Porphyromonas gingivalis ; Porphyromonas gingivalis - drug effects ; Porphyromonas gingivalis - enzymology ; Pretreatment ; Survival ; Survival factor ; Tissue culture ; Virulence ; Virulence factors</subject><ispartof>FEMS microbiology letters, 2006-11, Vol.264 (2), p.238-245</ispartof><rights>2006 Federation of European Microbiological Societies Published by Blackwell Publishing Ltd. All rights reserved 2006</rights><rights>2007 INIST-CNRS</rights><rights>2006 Federation of European Microbiological Societies Published by Blackwell Publishing Ltd. All rights reserved</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4688-a2c8de478c2c9fa9dc79d6713023235f5dcaeef45312a508108459aa4ee638c3</citedby><cites>FETCH-LOGICAL-c4688-a2c8de478c2c9fa9dc79d6713023235f5dcaeef45312a508108459aa4ee638c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1574-6968.2006.00458.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1574-6968.2006.00458.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27928,27929,45578,45579</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18213735$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16981905$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kobayashi-Sakamoto, Michiyo</creatorcontrib><creatorcontrib>Hirose, Kimiharu</creatorcontrib><creatorcontrib>Nishikata, Makoto</creatorcontrib><creatorcontrib>Isogai, Emiko</creatorcontrib><creatorcontrib>Chiba, Itsuo</creatorcontrib><title>Osteoprotegerin protects endothelial cells against apoptotic cell death induced by Porphyromonas gingivalis cysteine proteinases</title><title>FEMS microbiology letters</title><addtitle>FEMS Microbiol Lett</addtitle><description>Abstract
Osteoprotegerin (OPG) is a key regulator of osteoclastogenesis during the progression of periodontitis. Recent reports suggest that osteoprotegerin may also prevent arterial calcification and contribute to endothelial cell survival. To determine whether the vascular functions of osteoprotegerin are involved in periodontitis, we examined whether osteoprotegerin contributed to the survival of endothelial cells damaged by Porphyromonas gingivalis cysteine proteinases (gingipains). Gingipain proteinases cleave a broad range of host proteins, and are important virulence factors of P. gingivalis, a major causative bacterium of adult periodontitis. Human microvascular endothelial cells (HMVEC) were exposed to activated gingipain extracts from P. gingivalis 381, with and without pretreatment with osteoprotegerin. Cell viability was quantified by the tetrazolium (WST-8) reduction assay, and apoptosis was examined using Hoechst 33342 nuclear staining. After 16 h of treatment with activated gingipain extracts, HMVEC showed near-complete detachment from the tissue culture dish, and apoptosis was evident by 24 h. Pretreatment of HMVEC with osteoprotegerin reduced the extent of both cellular detachment and apoptotic cell death. Our results indicated that osteoprotegerin pretreatment protected HMVEC against detachment and apoptotic cell death induced by gingipain-active bacterial cell extracts. These results also suggest that osteoprotegerin may function as a survival factor for endothelial cells during periodontitis.</description><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - physiology</subject><subject>Arteriosclerosis</subject><subject>Bacteriology</subject><subject>Biological and medical sciences</subject><subject>Biomedical materials</subject><subject>Calcification</subject><subject>Calcification (ectopic)</subject><subject>Cell culture</subject><subject>Cell death</subject><subject>Cell survival</subject><subject>Cell viability</subject><subject>Cysteine</subject><subject>Cysteine Endopeptidases - pharmacology</subject><subject>Endothelial cells</subject><subject>Endothelial Cells - cytology</subject><subject>Endothelial Cells - drug effects</subject><subject>Endothelium, Vascular - cytology</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gingipain</subject><subject>gingipains</subject><subject>Humans</subject><subject>Microbiology</subject><subject>Microvasculature</subject><subject>Mortality</subject><subject>Osteoclastogenesis</subject><subject>Osteoprotegerin</subject><subject>Osteoprotegerin - metabolism</subject><subject>Osteoprotegerin - pharmacology</subject><subject>Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains</subject><subject>Periodontitis</subject><subject>Porphyromonas gingivalis</subject><subject>Porphyromonas gingivalis - drug effects</subject><subject>Porphyromonas gingivalis - enzymology</subject><subject>Pretreatment</subject><subject>Survival</subject><subject>Survival factor</subject><subject>Tissue culture</subject><subject>Virulence</subject><subject>Virulence factors</subject><issn>0378-1097</issn><issn>1574-6968</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkV-L1DAUxYMo7rj6FSQg-taaP22agC-yuCqMrA_7HrLp7UyGTlKTVrdvfnTT6eCCIpiXXHJ_J-fAQQhTUtJ83h5KWjdVIZSQJSNElIRUtSzvH6HN78VjtCG8kQUlqrlAz1I6kEwxIp6iCyqUpIrUG_TzJo0QhhhG2EF0Hp9GOyYMvg3jHnpnemyh7xM2O-N8GrEZwjCG0dnTO27BjHvsfDtZaPHdjL-GOOznGI7Bm4R3zu_cd9O7hO2czZyH1cTlLaTn6Eln-gQvzvclur3-cHv1qdjefPx89X5b2EpIWRhmZQtVIy2zqjOqtY1qRUM5YZzxuqtbawC6quaUmZpISmRVK2MqAMGl5Zfozfpttv42QRr10aUlvvEQpqSFVIorpjL46g_wEKboczTNOBF1JYkkmZIrZWNIKUKnh-iOJs6aEr1UpA96aUIvTeilIn2qSN9n6cuzwXR3hPZBeO4kA6_PgEnW9F003rr0wElGecMX7t3K_XA9zP8dQF9_2eYhy_kqD9PwD3Hxd_pfPx--mw</recordid><startdate>200611</startdate><enddate>200611</enddate><creator>Kobayashi-Sakamoto, Michiyo</creator><creator>Hirose, Kimiharu</creator><creator>Nishikata, Makoto</creator><creator>Isogai, Emiko</creator><creator>Chiba, Itsuo</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><general>Oxford University Press</general><scope>IQODW</scope><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>3V.</scope><scope>7QL</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200611</creationdate><title>Osteoprotegerin protects endothelial cells against apoptotic cell death induced by Porphyromonas gingivalis cysteine proteinases</title><author>Kobayashi-Sakamoto, Michiyo ; Hirose, Kimiharu ; Nishikata, Makoto ; Isogai, Emiko ; Chiba, Itsuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4688-a2c8de478c2c9fa9dc79d6713023235f5dcaeef45312a508108459aa4ee638c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - physiology</topic><topic>Arteriosclerosis</topic><topic>Bacteriology</topic><topic>Biological and medical sciences</topic><topic>Biomedical materials</topic><topic>Calcification</topic><topic>Calcification (ectopic)</topic><topic>Cell culture</topic><topic>Cell death</topic><topic>Cell survival</topic><topic>Cell viability</topic><topic>Cysteine</topic><topic>Cysteine Endopeptidases - pharmacology</topic><topic>Endothelial cells</topic><topic>Endothelial Cells - cytology</topic><topic>Endothelial Cells - drug effects</topic><topic>Endothelium, Vascular - cytology</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gingipain</topic><topic>gingipains</topic><topic>Humans</topic><topic>Microbiology</topic><topic>Microvasculature</topic><topic>Mortality</topic><topic>Osteoclastogenesis</topic><topic>Osteoprotegerin</topic><topic>Osteoprotegerin - metabolism</topic><topic>Osteoprotegerin - pharmacology</topic><topic>Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains</topic><topic>Periodontitis</topic><topic>Porphyromonas gingivalis</topic><topic>Porphyromonas gingivalis - drug effects</topic><topic>Porphyromonas gingivalis - enzymology</topic><topic>Pretreatment</topic><topic>Survival</topic><topic>Survival factor</topic><topic>Tissue culture</topic><topic>Virulence</topic><topic>Virulence factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kobayashi-Sakamoto, Michiyo</creatorcontrib><creatorcontrib>Hirose, Kimiharu</creatorcontrib><creatorcontrib>Nishikata, Makoto</creatorcontrib><creatorcontrib>Isogai, Emiko</creatorcontrib><creatorcontrib>Chiba, Itsuo</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>FEMS microbiology letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kobayashi-Sakamoto, Michiyo</au><au>Hirose, Kimiharu</au><au>Nishikata, Makoto</au><au>Isogai, Emiko</au><au>Chiba, Itsuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Osteoprotegerin protects endothelial cells against apoptotic cell death induced by Porphyromonas gingivalis cysteine proteinases</atitle><jtitle>FEMS microbiology letters</jtitle><addtitle>FEMS Microbiol Lett</addtitle><date>2006-11</date><risdate>2006</risdate><volume>264</volume><issue>2</issue><spage>238</spage><epage>245</epage><pages>238-245</pages><issn>0378-1097</issn><eissn>1574-6968</eissn><coden>FMLED7</coden><abstract>Abstract
Osteoprotegerin (OPG) is a key regulator of osteoclastogenesis during the progression of periodontitis. Recent reports suggest that osteoprotegerin may also prevent arterial calcification and contribute to endothelial cell survival. To determine whether the vascular functions of osteoprotegerin are involved in periodontitis, we examined whether osteoprotegerin contributed to the survival of endothelial cells damaged by Porphyromonas gingivalis cysteine proteinases (gingipains). Gingipain proteinases cleave a broad range of host proteins, and are important virulence factors of P. gingivalis, a major causative bacterium of adult periodontitis. Human microvascular endothelial cells (HMVEC) were exposed to activated gingipain extracts from P. gingivalis 381, with and without pretreatment with osteoprotegerin. Cell viability was quantified by the tetrazolium (WST-8) reduction assay, and apoptosis was examined using Hoechst 33342 nuclear staining. After 16 h of treatment with activated gingipain extracts, HMVEC showed near-complete detachment from the tissue culture dish, and apoptosis was evident by 24 h. Pretreatment of HMVEC with osteoprotegerin reduced the extent of both cellular detachment and apoptotic cell death. Our results indicated that osteoprotegerin pretreatment protected HMVEC against detachment and apoptotic cell death induced by gingipain-active bacterial cell extracts. These results also suggest that osteoprotegerin may function as a survival factor for endothelial cells during periodontitis.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>16981905</pmid><doi>10.1111/j.1574-6968.2006.00458.x</doi><tpages>8</tpages></addata></record> |
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| subjects | Apoptosis Apoptosis - drug effects Apoptosis - physiology Arteriosclerosis Bacteriology Biological and medical sciences Biomedical materials Calcification Calcification (ectopic) Cell culture Cell death Cell survival Cell viability Cysteine Cysteine Endopeptidases - pharmacology Endothelial cells Endothelial Cells - cytology Endothelial Cells - drug effects Endothelium, Vascular - cytology Endothelium, Vascular - drug effects Fundamental and applied biological sciences. Psychology Gingipain gingipains Humans Microbiology Microvasculature Mortality Osteoclastogenesis Osteoprotegerin Osteoprotegerin - metabolism Osteoprotegerin - pharmacology Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains Periodontitis Porphyromonas gingivalis Porphyromonas gingivalis - drug effects Porphyromonas gingivalis - enzymology Pretreatment Survival Survival factor Tissue culture Virulence Virulence factors |
| title | Osteoprotegerin protects endothelial cells against apoptotic cell death induced by Porphyromonas gingivalis cysteine proteinases |
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