Periodontal pathogen-related stimulation indicates unique phenotype of primary cultured human fibroblasts from gingiva and periodontal ligament: Implications for oral health disease
Identifieur interne : 000947 ( Istex/Corpus ); précédent : 000946; suivant : 000948Periodontal pathogen-related stimulation indicates unique phenotype of primary cultured human fibroblasts from gingiva and periodontal ligament: Implications for oral health disease
Auteurs : Sreenivas Koka ; Richard A. ReinhardtSource :
- The Journal of Prosthetic Dentistry [ 0022-3913 ] ; 1997.
English descriptors
- KwdEn :
- Active disease, Adult periodontitis, Alveolar bone loss, Assay, Bacterial virulence factors, Bone loss, Bone resorption, Cell population, Connective tissue, Culture supernatants, Cytokine, Dent, Dental implants, Dentistry, Edentulous patients, Extracellular matrix, Fibroblast, Fibroblast heterogeneity, Fibroblast subpopulations, Gentamicin sulfate, Gingival, Gingival fibroblasts, Gingivalis, Higher levels, Human gingival, Human gingival fibroblasts, Identical conditions, Implant, Independent variables, Inflammatory, Inflammatory mediator production, Inflammatory mediators, Interactive effects, Koka, Ligament, Ligament cells, Marginal bone height, Mediator, Mediator secretion, Mononuclear cells, Number2 koka, Oral maxillofac implants, Osseointegrated, Pdlf, Periodont, Periodontal, Periodontal disease, Periodontal ligament, Periodontal ligament cells, Periodontal ligament fibroblasts, Periodontal tissues, Periodontitis, Pge2, Pge2 levels, Pge2 production, Pge2 secretion, Predominant cell type, Prostaglandin, Prosthet dent, Prosthetic dentistry, Refractory periodontitis, Relevant group, Resorption, Tukey post, Unstimulated cells, Virulence factor.
- Teeft :
- Active disease, Adult periodontitis, Alveolar bone loss, Assay, Bacterial virulence factors, Bone loss, Bone resorption, Cell population, Connective tissue, Culture supernatants, Cytokine, Dent, Dental implants, Dentistry, Edentulous patients, Extracellular matrix, Fibroblast, Fibroblast heterogeneity, Fibroblast subpopulations, Gentamicin sulfate, Gingival, Gingival fibroblasts, Gingivalis, Higher levels, Human gingival, Human gingival fibroblasts, Identical conditions, Implant, Independent variables, Inflammatory, Inflammatory mediator production, Inflammatory mediators, Interactive effects, Koka, Ligament, Ligament cells, Marginal bone height, Mediator, Mediator secretion, Mononuclear cells, Number2 koka, Oral maxillofac implants, Osseointegrated, Pdlf, Periodont, Periodontal, Periodontal disease, Periodontal ligament, Periodontal ligament cells, Periodontal ligament fibroblasts, Periodontal tissues, Periodontitis, Pge2, Pge2 levels, Pge2 production, Pge2 secretion, Predominant cell type, Prostaglandin, Prosthet dent, Prosthetic dentistry, Refractory periodontitis, Relevant group, Resorption, Tukey post, Unstimulated cells, Virulence factor.
Abstract
Abstract: Statement of Problem. The fibroblast is considered an important cellular component in periodontitis because it is the predominant cell type in periodontal connective tissue. Purpose. The purpose of this study was to test whether gingival fibroblasts (GF) and periodontal ligament fibroblasts (PDLF) are heterogeneous in their production of inflammatory mediators associated with bone resorption in response to lipopolysaccharides from the gram-negative bacterium Porphyromonas gingivalis . To test this hypothesis, we (1) compared interleukin-6 production by cultured human PDLF and GF isolated from the same individual when exposed to P. gingivalis lipopolysaccharide; and (2) compared prostaglandin-E 2 production by cultured human PDLF and GF isolated from the same individual when exposed to P. gingivalis lipopolysaccharide. Material and Methods. Human periodontal ligament and gingival fibroblasts were cultured from biopsies and exposed to P. gingivalis lipopolysaccharide. Levels of interleukin-6 and prostaglandin-E 2 secreted into culture supernatant were measured by enzyme-linked immunosorbent assay and the data analyzed. Gingival fibroblasts secreted similar interleukin-6 and elevated prostaglandin-E 2 levels compared with unstimulated cells. Periodontal ligament fibroblasts secreted elevated levels of both mediators compared with unstimulated cells. Secreted levels of interleukin-6 and prostaglandin-E 2 by primary gingival and periodontal ligament fibroblast cultures appear to differ when stimulated with a periodontal pathogen-related virulence factor. Conclusion. The fibroblast of the periodontal ligament and the fibroblast of the gingiva may represent different phenotypes that play unique roles in tissue responses to implants. (J Prosthet Dent 1997:77:191-6.)
Url:
DOI: 10.1016/S0022-3913(97)70234-8
Links to Exploration step
ISTEX:12FF7F22DDAAB652B59E60A7DE1E00D065964F4CLe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Periodontal pathogen-related stimulation indicates unique phenotype of primary cultured human fibroblasts from gingiva and periodontal ligament: Implications for oral health disease</title><author><name sortKey="Koka, Sreenivas" sort="Koka, Sreenivas" uniqKey="Koka S" first="Sreenivas" last="Koka">Sreenivas Koka</name><affiliation><mods:affiliation>College of Dentistry, University of Nebraska Medical Center, Lincoln, Neb</mods:affiliation></affiliation></author><author><name sortKey="Reinhardt, Richard A" sort="Reinhardt, Richard A" uniqKey="Reinhardt R" first="Richard A." last="Reinhardt">Richard A. Reinhardt</name><affiliation><mods:affiliation>College of Dentistry, University of Nebraska Medical Center, Lincoln, Neb</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:12FF7F22DDAAB652B59E60A7DE1E00D065964F4C</idno><date when="1997" year="1997">1997</date><idno type="doi">10.1016/S0022-3913(97)70234-8</idno><idno type="url">https://api.istex.fr/document/12FF7F22DDAAB652B59E60A7DE1E00D065964F4C/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000947</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000947</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Periodontal pathogen-related stimulation indicates unique phenotype of primary cultured human fibroblasts from gingiva and periodontal ligament: Implications for oral health disease</title><author><name sortKey="Koka, Sreenivas" sort="Koka, Sreenivas" uniqKey="Koka S" first="Sreenivas" last="Koka">Sreenivas Koka</name><affiliation><mods:affiliation>College of Dentistry, University of Nebraska Medical Center, Lincoln, Neb</mods:affiliation></affiliation></author><author><name sortKey="Reinhardt, Richard A" sort="Reinhardt, Richard A" uniqKey="Reinhardt R" first="Richard A." last="Reinhardt">Richard A. Reinhardt</name><affiliation><mods:affiliation>College of Dentistry, University of Nebraska Medical Center, Lincoln, Neb</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">The Journal of Prosthetic Dentistry</title><title level="j" type="abbrev">YMPR</title><idno type="ISSN">0022-3913</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1997">1997</date><biblScope unit="volume">77</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="191">191</biblScope><biblScope unit="page" to="196">196</biblScope></imprint><idno type="ISSN">0022-3913</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-3913</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Active disease</term><term>Adult periodontitis</term><term>Alveolar bone loss</term><term>Assay</term><term>Bacterial virulence factors</term><term>Bone loss</term><term>Bone resorption</term><term>Cell population</term><term>Connective tissue</term><term>Culture supernatants</term><term>Cytokine</term><term>Dent</term><term>Dental implants</term><term>Dentistry</term><term>Edentulous patients</term><term>Extracellular matrix</term><term>Fibroblast</term><term>Fibroblast heterogeneity</term><term>Fibroblast subpopulations</term><term>Gentamicin sulfate</term><term>Gingival</term><term>Gingival fibroblasts</term><term>Gingivalis</term><term>Higher levels</term><term>Human gingival</term><term>Human gingival fibroblasts</term><term>Identical conditions</term><term>Implant</term><term>Independent variables</term><term>Inflammatory</term><term>Inflammatory mediator production</term><term>Inflammatory mediators</term><term>Interactive effects</term><term>Koka</term><term>Ligament</term><term>Ligament cells</term><term>Marginal bone height</term><term>Mediator</term><term>Mediator secretion</term><term>Mononuclear cells</term><term>Number2 koka</term><term>Oral maxillofac implants</term><term>Osseointegrated</term><term>Pdlf</term><term>Periodont</term><term>Periodontal</term><term>Periodontal disease</term><term>Periodontal ligament</term><term>Periodontal ligament cells</term><term>Periodontal ligament fibroblasts</term><term>Periodontal tissues</term><term>Periodontitis</term><term>Pge2</term><term>Pge2 levels</term><term>Pge2 production</term><term>Pge2 secretion</term><term>Predominant cell type</term><term>Prostaglandin</term><term>Prosthet dent</term><term>Prosthetic dentistry</term><term>Refractory periodontitis</term><term>Relevant group</term><term>Resorption</term><term>Tukey post</term><term>Unstimulated cells</term><term>Virulence factor</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Active disease</term><term>Adult periodontitis</term><term>Alveolar bone loss</term><term>Assay</term><term>Bacterial virulence factors</term><term>Bone loss</term><term>Bone resorption</term><term>Cell population</term><term>Connective tissue</term><term>Culture supernatants</term><term>Cytokine</term><term>Dent</term><term>Dental implants</term><term>Dentistry</term><term>Edentulous patients</term><term>Extracellular matrix</term><term>Fibroblast</term><term>Fibroblast heterogeneity</term><term>Fibroblast subpopulations</term><term>Gentamicin sulfate</term><term>Gingival</term><term>Gingival fibroblasts</term><term>Gingivalis</term><term>Higher levels</term><term>Human gingival</term><term>Human gingival fibroblasts</term><term>Identical conditions</term><term>Implant</term><term>Independent variables</term><term>Inflammatory</term><term>Inflammatory mediator production</term><term>Inflammatory mediators</term><term>Interactive effects</term><term>Koka</term><term>Ligament</term><term>Ligament cells</term><term>Marginal bone height</term><term>Mediator</term><term>Mediator secretion</term><term>Mononuclear cells</term><term>Number2 koka</term><term>Oral maxillofac implants</term><term>Osseointegrated</term><term>Pdlf</term><term>Periodont</term><term>Periodontal</term><term>Periodontal disease</term><term>Periodontal ligament</term><term>Periodontal ligament cells</term><term>Periodontal ligament fibroblasts</term><term>Periodontal tissues</term><term>Periodontitis</term><term>Pge2</term><term>Pge2 levels</term><term>Pge2 production</term><term>Pge2 secretion</term><term>Predominant cell type</term><term>Prostaglandin</term><term>Prosthet dent</term><term>Prosthetic dentistry</term><term>Refractory periodontitis</term><term>Relevant group</term><term>Resorption</term><term>Tukey post</term><term>Unstimulated cells</term><term>Virulence factor</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Statement of Problem. The fibroblast is considered an important cellular component in periodontitis because it is the predominant cell type in periodontal connective tissue. Purpose. The purpose of this study was to test whether gingival fibroblasts (GF) and periodontal ligament fibroblasts (PDLF) are heterogeneous in their production of inflammatory mediators associated with bone resorption in response to lipopolysaccharides from the gram-negative bacterium Porphyromonas gingivalis . To test this hypothesis, we (1) compared interleukin-6 production by cultured human PDLF and GF isolated from the same individual when exposed to P. gingivalis lipopolysaccharide; and (2) compared prostaglandin-E 2 production by cultured human PDLF and GF isolated from the same individual when exposed to P. gingivalis lipopolysaccharide. Material and Methods. Human periodontal ligament and gingival fibroblasts were cultured from biopsies and exposed to P. gingivalis lipopolysaccharide. Levels of interleukin-6 and prostaglandin-E 2 secreted into culture supernatant were measured by enzyme-linked immunosorbent assay and the data analyzed. Gingival fibroblasts secreted similar interleukin-6 and elevated prostaglandin-E 2 levels compared with unstimulated cells. Periodontal ligament fibroblasts secreted elevated levels of both mediators compared with unstimulated cells. Secreted levels of interleukin-6 and prostaglandin-E 2 by primary gingival and periodontal ligament fibroblast cultures appear to differ when stimulated with a periodontal pathogen-related virulence factor. Conclusion. The fibroblast of the periodontal ligament and the fibroblast of the gingiva may represent different phenotypes that play unique roles in tissue responses to implants. (J Prosthet Dent 1997:77:191-6.)</div></front></TEI><istex><corpusName>elsevier</corpusName><keywords><teeft><json:string>pdlf</json:string><json:string>fibroblast</json:string><json:string>periodontal</json:string><json:string>pge2</json:string><json:string>gingival</json:string><json:string>mediator</json:string><json:string>periodont</json:string><json:string>resorption</json:string><json:string>implant</json:string><json:string>bone resorption</json:string><json:string>periodontitis</json:string><json:string>prostaglandin</json:string><json:string>osseointegrated</json:string><json:string>ligament</json:string><json:string>periodontal disease</json:string><json:string>gingivalis</json:string><json:string>koka</json:string><json:string>cytokine</json:string><json:string>periodontal ligament</json:string><json:string>gingival fibroblasts</json:string><json:string>assay</json:string><json:string>pge2 production</json:string><json:string>oral maxillofac implants</json:string><json:string>prosthetic dentistry</json:string><json:string>pge2 secretion</json:string><json:string>dentistry</json:string><json:string>inflammatory</json:string><json:string>inflammatory mediators</json:string><json:string>culture supernatants</json:string><json:string>interactive effects</json:string><json:string>gentamicin sulfate</json:string><json:string>pge2 levels</json:string><json:string>connective tissue</json:string><json:string>extracellular matrix</json:string><json:string>human gingival fibroblasts</json:string><json:string>dent</json:string><json:string>periodontal tissues</json:string><json:string>higher levels</json:string><json:string>inflammatory mediator production</json:string><json:string>identical conditions</json:string><json:string>virulence factor</json:string><json:string>unstimulated cells</json:string><json:string>number2 koka</json:string><json:string>mediator secretion</json:string><json:string>periodontal ligament fibroblasts</json:string><json:string>cell population</json:string><json:string>dental implants</json:string><json:string>predominant cell type</json:string><json:string>independent variables</json:string><json:string>tukey post</json:string><json:string>relevant group</json:string><json:string>prosthet dent</json:string><json:string>fibroblast heterogeneity</json:string><json:string>active disease</json:string><json:string>alveolar bone loss</json:string><json:string>bone loss</json:string><json:string>marginal bone height</json:string><json:string>edentulous patients</json:string><json:string>periodontal ligament cells</json:string><json:string>mononuclear cells</json:string><json:string>human gingival</json:string><json:string>adult periodontitis</json:string><json:string>ligament cells</json:string><json:string>fibroblast subpopulations</json:string><json:string>bacterial virulence factors</json:string><json:string>refractory periodontitis</json:string></teeft></keywords><author><json:item><name>Sreenivas Koka DDS, MSa</name><affiliations><json:string>College of Dentistry, University of Nebraska Medical Center, Lincoln, Neb</json:string></affiliations></json:item><json:item><name>Richard A. Reinhardt DDS, MS, PhDb</name><affiliations><json:string>College of Dentistry, University of Nebraska Medical Center, Lincoln, Neb</json:string></affiliations></json:item></author><arkIstex>ark:/67375/6H6-DF0V9S75-M</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><abstract>Abstract: Statement of Problem. The fibroblast is considered an important cellular component in periodontitis because it is the predominant cell type in periodontal connective tissue. Purpose. The purpose of this study was to test whether gingival fibroblasts (GF) and periodontal ligament fibroblasts (PDLF) are heterogeneous in their production of inflammatory mediators associated with bone resorption in response to lipopolysaccharides from the gram-negative bacterium Porphyromonas gingivalis . To test this hypothesis, we (1) compared interleukin-6 production by cultured human PDLF and GF isolated from the same individual when exposed to P. gingivalis lipopolysaccharide; and (2) compared prostaglandin-E 2 production by cultured human PDLF and GF isolated from the same individual when exposed to P. gingivalis lipopolysaccharide. Material and Methods. Human periodontal ligament and gingival fibroblasts were cultured from biopsies and exposed to P. gingivalis lipopolysaccharide. Levels of interleukin-6 and prostaglandin-E 2 secreted into culture supernatant were measured by enzyme-linked immunosorbent assay and the data analyzed. Gingival fibroblasts secreted similar interleukin-6 and elevated prostaglandin-E 2 levels compared with unstimulated cells. Periodontal ligament fibroblasts secreted elevated levels of both mediators compared with unstimulated cells. Secreted levels of interleukin-6 and prostaglandin-E 2 by primary gingival and periodontal ligament fibroblast cultures appear to differ when stimulated with a periodontal pathogen-related virulence factor. Conclusion. The fibroblast of the periodontal ligament and the fibroblast of the gingiva may represent different phenotypes that play unique roles in tissue responses to implants. (J Prosthet Dent 1997:77:191-6.)</abstract><qualityIndicators><score>9.084</score><pdfWordCount>4240</pdfWordCount><pdfCharCount>27224</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>6</pdfPageCount><pdfPageSize>576 x 792 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>237</abstractWordCount><abstractCharCount>1798</abstractCharCount><keywordCount>0</keywordCount></qualityIndicators><title>Periodontal pathogen-related stimulation indicates unique phenotype of primary cultured human fibroblasts from gingiva and periodontal ligament: Implications for oral health disease</title><pmid><json:string>9051608</json:string></pmid><pii><json:string>S0022-3913(97)70234-8</json:string></pii><genre><json:string>research-article</json:string></genre><serie><title>Methods of enzymology: complex carbohydrates.</title><language><json:string>unknown</json:string></language><pages><first>3</first><last>26</last></pages></serie><host><title>The Journal of Prosthetic Dentistry</title><language><json:string>unknown</json:string></language><publicationDate>1997</publicationDate><issn><json:string>0022-3913</json:string></issn><pii><json:string>S0022-3913(05)X7037-8</json:string></pii><volume>77</volume><issue>2</issue><pages><first>191</first><last>196</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>1997</json:string><json:string>1996</json:string></date><geogName><json:string>Ill</json:string></geogName><orgName><json:string>PerSeptive Diagnostics, Cambridge</json:string><json:string>Pierce Chemical Corp.</json:string><json:string>Immunoregulation Laboratories</json:string><json:string>BioWhittaker, Inc.</json:string><json:string>Sigma Chemical Co.</json:string><json:string>Bio-Rad Laboratories, Inc</json:string><json:string>Academy of Prosthodontics</json:string></orgName><orgName_funder></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Professor</json:string><json:string>Ann Moran</json:string><json:string>I. Human</json:string></persName><placeName><json:string>Mass.</json:string><json:string>France</json:string><json:string>Calif.</json:string><json:string>Cambridge</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>Prabhu et al.</json:string><json:string>Reinhardt et al.</json:string><json:string>Somerman et al.</json:string><json:string>Shimizu et al.</json:string><json:string>Brunk et al.</json:string><json:string>Geivelis et al.</json:string><json:string>Schifferle et al.</json:string><json:string>Takahashi et al.</json:string><json:string>Fries et al.</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/6H6-DF0V9S75-M</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - dentistry, oral surgery & medicine</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - clinical medicine</json:string><json:string>3 - dentistry</json:string></scienceMetrix><scopus><json:string>1 - Health Sciences</json:string><json:string>2 - Dentistry</json:string><json:string>3 - Oral Surgery</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string></inist></categories><publicationDate>1997</publicationDate><copyrightDate>1997</copyrightDate><doi><json:string>10.1016/S0022-3913(97)70234-8</json:string></doi><id>12FF7F22DDAAB652B59E60A7DE1E00D065964F4C</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/12FF7F22DDAAB652B59E60A7DE1E00D065964F4C/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/12FF7F22DDAAB652B59E60A7DE1E00D065964F4C/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/12FF7F22DDAAB652B59E60A7DE1E00D065964F4C/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Periodontal pathogen-related stimulation indicates unique phenotype of primary cultured human fibroblasts from gingiva and periodontal ligament: Implications for oral health disease</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>ELSEVIER</publisher><availability><p>©1997 Editorial Council of the Journal of Prosthetic Dentistry</p></availability><date>1997</date></publicationStmt><notesStmt><note>a Assistant Professor, Immunoregulation Laboratories.</note><note>b Bernard and Ann Moran Professor of Periodontics, Immunoregulation Laboratories.</note><note>Reprint requests to: Dr. Sreenivas Koka Immunoregulation Laboratories College of Dentistry University of Nebraska Medical Center 40th and Holdrege Streets Lincoln, NE 68583-0740</note><note>0022-3913/97/$5.00 + 0 10/1/79110</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Periodontal pathogen-related stimulation indicates unique phenotype of primary cultured human fibroblasts from gingiva and periodontal ligament: Implications for oral health disease</title><author xml:id="author-0000"><persName><forename type="first">Sreenivas</forename><surname>Koka</surname></persName><roleName type="degree">DDS, MSa</roleName><affiliation>College of Dentistry, University of Nebraska Medical Center, Lincoln, Neb</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Richard A.</forename><surname>Reinhardt</surname></persName><roleName type="degree">DDS, MS, PhDb</roleName><affiliation>College of Dentistry, University of Nebraska Medical Center, Lincoln, Neb</affiliation></author><idno type="istex">12FF7F22DDAAB652B59E60A7DE1E00D065964F4C</idno><idno type="DOI">10.1016/S0022-3913(97)70234-8</idno><idno type="PII">S0022-3913(97)70234-8</idno></analytic><monogr><title level="j">The Journal of Prosthetic Dentistry</title><title level="j" type="abbrev">YMPR</title><idno type="pISSN">0022-3913</idno><idno type="PII">S0022-3913(05)X7037-8</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1997"></date><biblScope unit="volume">77</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="191">191</biblScope><biblScope unit="page" to="196">196</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1997</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Statement of Problem. The fibroblast is considered an important cellular component in periodontitis because it is the predominant cell type in periodontal connective tissue. Purpose. The purpose of this study was to test whether gingival fibroblasts (GF) and periodontal ligament fibroblasts (PDLF) are heterogeneous in their production of inflammatory mediators associated with bone resorption in response to lipopolysaccharides from the gram-negative bacterium Porphyromonas gingivalis . To test this hypothesis, we (1) compared interleukin-6 production by cultured human PDLF and GF isolated from the same individual when exposed to P. gingivalis lipopolysaccharide; and (2) compared prostaglandin-E 2 production by cultured human PDLF and GF isolated from the same individual when exposed to P. gingivalis lipopolysaccharide. Material and Methods. Human periodontal ligament and gingival fibroblasts were cultured from biopsies and exposed to P. gingivalis lipopolysaccharide. Levels of interleukin-6 and prostaglandin-E 2 secreted into culture supernatant were measured by enzyme-linked immunosorbent assay and the data analyzed. Gingival fibroblasts secreted similar interleukin-6 and elevated prostaglandin-E 2 levels compared with unstimulated cells. Periodontal ligament fibroblasts secreted elevated levels of both mediators compared with unstimulated cells. Secreted levels of interleukin-6 and prostaglandin-E 2 by primary gingival and periodontal ligament fibroblast cultures appear to differ when stimulated with a periodontal pathogen-related virulence factor. Conclusion. The fibroblast of the periodontal ligament and the fibroblast of the gingiva may represent different phenotypes that play unique roles in tissue responses to implants. (J Prosthet Dent 1997:77:191-6.)</p></abstract></profileDesc><revisionDesc><change when="1997">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/12FF7F22DDAAB652B59E60A7DE1E00D065964F4C/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier doc found" wicri:toSee="Elsevier, no converted or simple article"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 5.0.1//EN//XML" URI="art501.dtd" name="istex:docType"><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity><istex:entity SYSTEM="gr3" NDATA="IMAGE" name="gr3"></istex:entity><istex:entity SYSTEM="gr4" NDATA="IMAGE" name="gr4"></istex:entity></istex:docType><istex:document><article docsubtype="fla" xml:lang="en"><item-info><jid>YMPR</jid><aid>79110</aid><ce:pii>S0022-3913(97)70234-8</ce:pii><ce:doi>10.1016/S0022-3913(97)70234-8</ce:doi><ce:copyright type="other" year="1997">Editorial Council of the Journal of Prosthetic Dentistry</ce:copyright></item-info><head><ce:article-footnote><ce:label>☆</ce:label><ce:note-para><ce:sup>a</ce:sup> Assistant Professor, Immunoregulation Laboratories.</ce:note-para></ce:article-footnote><ce:article-footnote><ce:label>☆☆</ce:label><ce:note-para><ce:sup>b</ce:sup> Bernard and Ann Moran Professor of Periodontics, Immunoregulation Laboratories.</ce:note-para></ce:article-footnote><ce:article-footnote><ce:label>★</ce:label><ce:note-para><ce:italic>Reprint requests to:</ce:italic> <ce:small-caps>Dr. Sreenivas Koka Immunoregulation Laboratories College of Dentistry University of Nebraska Medical Center 40th and Holdrege Streets Lincoln, NE 68583-0740</ce:small-caps></ce:note-para></ce:article-footnote><ce:article-footnote><ce:label>★★</ce:label><ce:note-para>0022-3913/97/$5.00 + 0 <ce:bold>10/1/79110</ce:bold></ce:note-para></ce:article-footnote><ce:title>Periodontal pathogen-related stimulation indicates unique phenotype of primary cultured human fibroblasts from gingiva and periodontal ligament: Implications for oral health disease</ce:title><ce:presented>Presented at the 78th Annual Meeting of the Academy of Prosthodontics, Newport Beach, California, May 1996.</ce:presented><ce:author-group><ce:author><ce:given-name>Sreenivas</ce:given-name><ce:surname>Koka</ce:surname><ce:degrees>DDS, MS<ce:sup>a</ce:sup></ce:degrees></ce:author><ce:author><ce:given-name>Richard A.</ce:given-name><ce:surname>Reinhardt</ce:surname><ce:degrees>DDS, MS, PhD<ce:sup>b</ce:sup></ce:degrees></ce:author><ce:affiliation><ce:textfn>College of Dentistry, University of Nebraska Medical Center, Lincoln, Neb</ce:textfn></ce:affiliation></ce:author-group><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para><ce:bold>Statement of Problem.</ce:bold> The fibroblast is considered an important cellular component in periodontitis because it is the predominant cell type in periodontal connective tissue.</ce:simple-para><ce:simple-para><ce:bold>Purpose.</ce:bold> The purpose of this study was to test whether gingival fibroblasts (GF) and periodontal ligament fibroblasts (PDLF) are heterogeneous in their production of inflammatory mediators associated with bone resorption in response to lipopolysaccharides from the gram-negative bacterium <ce:italic>Porphyromonas gingivalis</ce:italic> . To test this hypothesis, we (1) compared interleukin-6 production by cultured human PDLF and GF isolated from the same individual when exposed to <ce:italic>P. gingivalis</ce:italic> lipopolysaccharide; and (2) compared prostaglandin-E
<ce:inf>2</ce:inf> production by cultured human PDLF and GF isolated from the same individual when exposed to <ce:italic>P. gingivalis</ce:italic> lipopolysaccharide.</ce:simple-para><ce:simple-para><ce:bold>Material and Methods.</ce:bold> Human periodontal ligament and gingival fibroblasts were cultured from biopsies and exposed to <ce:italic>P. gingivalis</ce:italic> lipopolysaccharide. Levels of interleukin-6 and prostaglandin-E
<ce:inf>2</ce:inf> secreted into culture supernatant were measured by enzyme-linked immunosorbent assay and the data analyzed. Gingival fibroblasts secreted similar interleukin-6 and elevated prostaglandin-E
<ce:inf>2</ce:inf> levels compared with unstimulated cells. Periodontal ligament fibroblasts secreted elevated levels of both mediators compared with unstimulated cells. Secreted levels of interleukin-6 and prostaglandin-E
<ce:inf>2</ce:inf> by primary gingival and periodontal ligament fibroblast cultures appear to differ when stimulated with a periodontal pathogen-related virulence factor.</ce:simple-para><ce:simple-para><ce:bold>Conclusion.</ce:bold> The fibroblast of the periodontal ligament and the fibroblast of the gingiva may represent different phenotypes that play unique roles in tissue responses to implants. (J Prosthet Dent 1997:77:191-6.)</ce:simple-para></ce:abstract-sec></ce:abstract></head><body><ce:sections><ce:para><ce:display><ce:textbox><ce:textbox-body><ce:sections><ce:para><ce:bold><ce:italic>Osseointegration predicates a periodontal ligament-free interface between titanium dental implants and bone. The absence of a periodontal ligament adjacent to titanium screw endosteal dental implants may aid in maintaining periimplant bone height. Additional research into inflammatory mediator production by subpopulations of cells within gingival connective tissue and the periodontal ligament is indicated, with a long-term goal of selective stimulation of fibroblast subpopulations capable of inhibiting bone resorption and promoting wound healing.</ce:italic></ce:bold></ce:para></ce:sections></ce:textbox-body></ce:textbox></ce:display></ce:para><ce:para>Periodontal disease includes a wide range of inflammatory conditions of the periodontium, from early gingivitis to chronic periodontitis, and represents the major cause of edentulism. <ce:cross-ref refid="bib1"><ce:sup>1</ce:sup></ce:cross-ref> Crucial to the development and progression of periodontitis are local inflammatory mediators produced by cells of the periodontal lesion. <ce:cross-refs refid="bib2 bib3 bib4"><ce:sup>2-4</ce:sup></ce:cross-refs> Cells of the periodontal ligament have been implicated in the bone resorption process, with both fibroblasts and mononuclear cells suggested as playing a role in bone degradation. <ce:cross-ref refid="bib2"><ce:sup>2</ce:sup></ce:cross-ref> The fibroblast is considered an important cellular component in periodontitis because it is the predominant cell type in periodontal connective tissue. In the periodontitis lesion, these cells are likely to encounter cytokines and bacterial virulence factors, including lipopolysaccharide (LPS) from the prime periodontitis pathogen, <ce:italic>Porphyromonas gingivalis</ce:italic> . <ce:cross-ref refid="bib2"><ce:sup>2</ce:sup></ce:cross-ref> Fibroblast responses to LPS and certain cytokines include (1) an increase in the production of metalloproteinase enzymes capable of degrading the extracellular matrix, <ce:cross-refs refid="bib5 bib6 bib7 bib8 bib9"><ce:sup>5-9</ce:sup></ce:cross-refs> (2) a decrease in the production of enzymes that inhibit degradation of the extracellular matrix, <ce:cross-ref refid="bib10"><ce:sup>10</ce:sup></ce:cross-ref> and (3) an increase in the production of mediators of connective tissue and alveolar bone destruction. <ce:cross-refs refid="bib5 bib6 bib7 bib8 bib9 bib11 bib12"><ce:sup>5-9,11,12</ce:sup></ce:cross-refs> Two such mediators that form the focus of this study, the cytokine interleukin-6 (IL-6) and the arachidonic acid metabolite prostaglandin-E
<ce:inf>2</ce:inf> (PGE2), have been implicated in the pathogenesis of periodontal disease and, in particular, have been associated with bone resorption. <ce:cross-refs refid="bib13 bib14 bib15"><ce:sup>13-15</ce:sup></ce:cross-refs></ce:para><ce:para>IL-6 is a multifunctional protein that mediates inflammatory reactions and is expressed by many cell types, both constitutively and after activation. <ce:cross-ref refid="bib16"><ce:sup>16</ce:sup></ce:cross-ref> IL-6 promotes bone resorption by inhibiting collagen synthesis by osteoblasts <ce:cross-ref refid="bib17"><ce:sup>17</ce:sup></ce:cross-ref> and inducing osteoclast precursor recruitment and differentiation. <ce:cross-ref refid="bib18"><ce:sup>18</ce:sup></ce:cross-ref> IL-6 produced by calvarial osteoblasts has been shown to induce bone resorption, both alone and in concert with interleukin-1 (IL-1) and LPS. <ce:cross-ref refid="bib13"><ce:sup>13</ce:sup></ce:cross-ref> Bone resorption is considered an important factor in periodontal disease and alveolar bone loss. IL-6 production by human gingival cells and periodontal ligament cells is unregulated by exposure to LPS. <ce:cross-ref refid="bib11"><ce:sup>11</ce:sup></ce:cross-ref> Additionally, increased IL-6 concentration in gingival crevicular fluid (GCF) has been associated with patients with refractory periodontitis, <ce:cross-ref refid="bib19"><ce:sup>19</ce:sup></ce:cross-ref> and IL-6 has been positively correlated to bleeding index and probing depth in patients with adult periodontitis. <ce:cross-ref refid="bib20"><ce:sup>20</ce:sup></ce:cross-ref> After examination of inflamed gingival tissues, Takahashi et al. <ce:cross-ref refid="bib21"><ce:sup>21</ce:sup></ce:cross-ref> demonstrated increased IL-6 messenger ribonucleic acid and protein, notably in macrophages and fibroblasts, and suggested a strong association between the presence of IL-6 and periodontal inflammation and alveolar bone loss. More recently, Prabhu et al. <ce:cross-ref refid="bib22"><ce:sup>22</ce:sup></ce:cross-ref> confirmed elevated IL-6 messenger ribonucleic acid in tissues derived from clinically diseased periodontal connective tissue.</ce:para><ce:para>PGE2 is synthesized from arachidonic acid, a lipid within mammalian cell membranes. Arachidonic acid metabolism by cyclooxygenase metabolic pathway ultimately results in the synthesis of PGE2. <ce:cross-ref refid="bib23"><ce:sup>23</ce:sup></ce:cross-ref> PGE2 has a range of proinflammatory actions that includes vasodilation and increased capillary permeability, which lead to clinical signs such as redness and edema; it also acts as a chemoattractant. <ce:cross-ref refid="bib24"><ce:sup>24</ce:sup></ce:cross-ref> Bone resorptive effects of PGE2 include increased activity and mobility of osteoclasts, and the resultant effects in bone organ culture confirm that PGE2 can be a potent inducer of bone resorption. <ce:cross-refs refid="bib15 bib25 bib26"><ce:sup>15,25,26</ce:sup></ce:cross-refs> LPS is known to stimulate PGE2 secretion by monocytes <ce:cross-ref refid="bib27"><ce:sup>27</ce:sup></ce:cross-ref> and fibroblasts <ce:cross-ref refid="bib28"><ce:sup>28</ce:sup></ce:cross-ref> derived from periodontal tissues, and higher levels of PGE2 are found in diseased tissue than in clinically healthy biopsies. <ce:cross-ref refid="bib14"><ce:sup>14</ce:sup></ce:cross-ref></ce:para><ce:para>Two periodontal tissue compartments are important sources of fibroblasts and inflammatory mediators secreted by fibroblasts: the gingival connective tissue and the periodontal ligament. Recent studies suggest that fibroblasts from these two sources may be phenotypically heterogeneous in their response to various stimuli and that subtypes likely exist within gingival fibroblast (GF) and periodontal ligament fibroblast (PDLF) populations. <ce:cross-refs refid="bib29 bib30 bib31"><ce:sup>29-31</ce:sup></ce:cross-refs> Studies that have described oral fibroblast inflammatory mediator production have focused on both GF and PDLF, with PDLF studies gaining recent popularity. Both GF and PDLF are capable of secreting IL-6 and PGE2 in response to a range of stimuli, including LPS and cytokine exposure. <ce:cross-refs refid="bib9 bib11 bib12 bib28 bib30 bib32 bib33"><ce:sup>9,11,12,28,30,32,33</ce:sup></ce:cross-refs> However, valid comparison of GF and PDLF activity is impossible if the two groups of cells are isolated from different subjects or if the two cell types are exposed to dissimilar culturing conditions. No reports of inflammatory mediator production by GF and PDLF of the same individual that were cultured under identical conditions seem to appear.</ce:para><ce:para>The purpose of this study was to test whether GF and PDLF are heterogeneous in their production of IL-6 and PGE2 in response to the periodontitis-associated virulence factor <ce:italic>P. gingivalis</ce:italic> LPS. Specific aims were developed to test this hypothesis: (1) to compare bone-resorptive cytokine (IL-6) production by cultured human PDLF and GF isolated from the same individual when exposed to <ce:italic>P. gingivalis</ce:italic> LPS, and (2) to compare bone-resorptive mediator (PGE2) production by cultured human PDLF and GF isolated from the same individual when exposed to <ce:italic>P. gingivalis</ce:italic> LPS.</ce:para><ce:section><ce:section-title>MATERIAL AND METHODS</ce:section-title><ce:section><ce:section-title>LPS preparation</ce:section-title><ce:para>LPS from <ce:italic>P. gingivalis</ce:italic> (ATCC 33277) were obtained from a procedure outlined by Schifferle et al. <ce:cross-ref refid="bib34"><ce:sup>34</ce:sup></ce:cross-ref> The resultant material was dialyzed against pyrogen-free distilled water, lyophilized, and confirmed as LPS by the Kineric-QCL test (BioWhittaker, Inc., Walkersville, Md.), with purified commercially prepared <ce:italic>Escherichia coli</ce:italic> LPS (Sigma Chemical Co., St. Louis, Mo.) as the control. Purified LPS from <ce:italic>P. gingivalis</ce:italic> contained only a trace amount of protein (<1%) according to the bicinchoninic acid (BCA) protein assay (Pierce Chemical Corp., Rockford, Ill.). Carbohydrate content of the LPS was 2%, as measured by the anthrone test. <ce:cross-ref refid="bib35"><ce:sup>35</ce:sup></ce:cross-ref> The LPS demonstrated a typical ladder-like LPS pattern on gel after polyacrylamide electrophoresis and silver staining (Bio-Rad Laboratories, Inc, Hercules, Calif.). <ce:cross-ref refid="bib36"><ce:sup>36</ce:sup></ce:cross-ref></ce:para></ce:section><ce:section><ce:section-title>Cell culture methods</ce:section-title><ce:para>Human PDLF were grown from tissue from the middle third of roots of third molars extracted from healthy donors as described by Somerman et al. <ce:cross-ref refid="bib29"><ce:sup>29</ce:sup></ce:cross-ref> and in accordance with Institutional Review Board informed consent. Concurrently, gingival biopsies from clinically noninflamed tissue of the same donors were obtained. GF and PDLF from three subjects were cultured according to a method modified from Shimizu et al. <ce:cross-ref refid="bib30"><ce:sup>30</ce:sup></ce:cross-ref> Tissue fragments of 1 mm <ce:sup>3</ce:sup> were individually plated in 16 mm wells, allowed to attach to the plastic surface by air drying for 20 minutes, and covered with 1 ml of alpha-minimum essential medium (alpha-MEM, Gibco, Paisley, Scotland) supplemented with 500 μg/ml penicillin G, 250 μg/ml gentamicin sulfate, 0.6 μg/ml amphotericin B, and 15% fetal bovine serum (FBS). The plates were incubated undisturbed at 37° C in a humidified atmosphere of 5% carbon dioxide for 1 week, after which the medium was decanted and replaced with alpha-MEM supplemented with 100 μg/ml penicillin G, 50 μg/ml gentamicin sulfate, 0.6 μg/ml amphotericin B, and 5% FBS. Medium was replenished every 3 days as GF and PDLF were passaged and expanded into T-75 tissue culture flasks (Falcon, Meylan Cedex, France).</ce:para><ce:para>GF and PDLF were passaged under identical conditions by removing existing medium and washing three times with fresh alpha-MEM before treatment with 0.25% trypsin/1 mmol EDTA solution in phosphate-buffered saline solution for 10 to 15 minutes. Cells from the third passage were plated in 16 mm plastic wells at a concentration of 10 <ce:sup>5</ce:sup> cells/well and left for 24 hours in 1 ml alpha-MEM supplemented with 100 μg/ml penicillin G, 50 μg/ml gentamicin sulfate, 0.6 μg/ml amphotericin B, and 0.2% FBS (alpha-MEM-A). At this time (time zero), the medium was replaced with 1 ml of alpha-MEM-A that contained either 1 μg/ml or 10 μg/ml of <ce:italic>P. gingivalis</ce:italic> LPS. The two concentrations of LPS were chosen to provide comparison with previous studies investigating inflammatory mediator secretion by oral fibroblasts. <ce:cross-refs refid="bib9 bib11 bib12 bib28"><ce:sup>9,11,12,28</ce:sup></ce:cross-refs> Cultures with alpha-MEM-A (without LPS) alone provided negative controls. Each subject's cells were cultured separately, and all experimental culturing conditions were run in triplicate. Supernatants, collected after 48 and 72 hours, were frozen at 70° C.</ce:para></ce:section><ce:section><ce:section-title>DNA assay</ce:section-title><ce:para>The DNA content of adherent fibroblasts was measured by a fluorimetric assay outlined by Brunk et al. <ce:cross-ref refid="bib37"><ce:sup>37</ce:sup></ce:cross-ref> to account for variability in fibroblast proliferation. Results were recorded as picograms of metabolite per milliliter of medium per microgram of DNA.</ce:para></ce:section><ce:section><ce:section-title>Enzyme immunoassays for IL-6 and PGE2</ce:section-title><ce:para>Commercially available enzyme-linked immunosorbent assays (ELISAs) were used to detect IL-6 (Genzyme, Cambridge, Mass.) and PGE2 (PerSeptive Diagnostics, Cambridge, Mass.) according to the manufacturers' instructions. The IL-6 assay relies on a double antibody sandwich technique, whereas PGE2 competes for a known amount of alkaline phosphatase-labeled PGE2. Duplicate assays of triplicate samples of each tested condition were performed. The minimum detectable concentrations were >18 pg/ml IL-6 and >1.5 pg/ml PGE2.</ce:para></ce:section><ce:section><ce:section-title>Statistical analysis</ce:section-title><ce:para>A three-way analysis of variance (ANOVA) was used to test for the effect of cell population, LPS concentration, and time of exposure on mediator secretion. Differences between group means were determined with Tukey's post hoc test ( <ce:italic>p</ce:italic> < 0.05).</ce:para></ce:section></ce:section><ce:section><ce:section-title>RESULTS</ce:section-title><ce:section><ce:section-title>IL-6</ce:section-title><ce:para><ce:cross-refs refid="fig1 fig2">Figures 1 and 2</ce:cross-refs> show IL-6 levels in culture supernatant; data are reported as picograms of IL-6 per milliliter of medium per microgram of DNA.
<ce:display><ce:figure id="fig1"><ce:label>Fig. 1</ce:label><ce:caption><ce:simple-para>IL-6 production in culture supernatants after 48 hours of stimulation with <ce:italic>P. gingivalis</ce:italic> LPS.</ce:simple-para></ce:caption> <ce:link locator="gr1"></ce:link></ce:figure></ce:display><ce:display><ce:figure id="fig2"><ce:label>Fig. 2</ce:label><ce:caption><ce:simple-para>IL-6 production in culture supernatants after 72 hours of stimulation with <ce:italic>P. gingivalis</ce:italic> LPS.</ce:simple-para></ce:caption> <ce:link locator="gr2"></ce:link></ce:figure></ce:display>A three-way ANOVA demonstrated that the effects of cell population, LPS concentration, and time of exposure on IL-6 secretion were each statistically significant ( <ce:italic>p</ce:italic> < 0.0001). Interactive effects ( <ce:italic>p</ce:italic> < 0.0001) were present among all combinations of independent variables. Tukey post hoc test ( <ce:italic>p</ce:italic> < 0.05) for differences between relevant group means revealed a dose- and time-dependent increase in IL-6 secretion by PDLF but not by GF. Unstimulated GF produced moderate levels of IL-6 that remained statistically similar when exposed to LPS.</ce:para></ce:section><ce:section><ce:section-title>PGE2</ce:section-title><ce:para><ce:cross-refs refid="fig3 fig4">Figures 3 and 4</ce:cross-refs> show PGE2 levels in culture supernatant; data are reported as picograms of PGE2 per milliliter of medium per microgram of DNA.
<ce:display><ce:figure id="fig3"><ce:label>Fig. 3</ce:label><ce:caption><ce:simple-para>PGE2 production in culture supernatants after 48 hours of stimulation with <ce:italic>P. gingivalis</ce:italic> LPS.</ce:simple-para></ce:caption> <ce:link locator="gr3"></ce:link></ce:figure></ce:display><ce:display><ce:figure id="fig4"><ce:label>Fig. 4</ce:label><ce:caption><ce:simple-para>PGE2 production in culture supernatants after 72 hours of stimulation with <ce:italic>P. gingivalis</ce:italic> LPS.</ce:simple-para></ce:caption> <ce:link locator="gr4"></ce:link></ce:figure></ce:display>A three-way ANOVA revealed that the effects of cell population, LPS concentration, and time of exposure on PGE2 secretion were each statistically significant ( <ce:italic>p</ce:italic> < 0.0001). Interactive effects ( <ce:italic>p</ce:italic> < 0.0001) were present among all combinations of independent variables. Tukey post hoc test ( <ce:italic>p</ce:italic> < 0.05) for differences between relevant group means revealed a dose- and time-dependent increase in PGE2 secretion by both PDLF and GF, with a significantly enhanced response of PDLF ( <ce:italic>p</ce:italic> < 0.05).</ce:para><ce:para>DNA assays demonstrated no indication of increased proliferation in response to LPS.</ce:para></ce:section></ce:section><ce:section><ce:section-title>DISCUSSION</ce:section-title><ce:para>The purpose of this study was to test whether GF and PDLF are heterogeneous in their production of IL-6 and PGE2 in response to a periodontitis-associated virulence factor, namely LPS, from the gram-negative bacterium <ce:italic>P. gingivalis</ce:italic> LPS. In the review of PDLF and GF studies, Fries et al. <ce:cross-ref refid="bib31"><ce:sup>31</ce:sup></ce:cross-ref> concluded that fibroblast heterogeneity exists within and between GF and PDLF populations. <ce:cross-refs refid="bib38 bib39 bib40 bib41 bib42 bib43"><ce:sup>38-43</ce:sup></ce:cross-refs> However, until now comparative studies that involve GF and PDLF have tested cells from different individuals or cell lines. <ce:cross-refs refid="bib6 bib28 bib30"><ce:sup>6,28,30</ce:sup></ce:cross-refs> This study represents the first report of inflammatory mediator secretion by GF and PDLF derived from the same individual and under identical culturing conditions. The results of this study support Fries et al. <ce:cross-ref refid="bib31"><ce:sup>31</ce:sup></ce:cross-ref> in that on stimulation with LPS from <ce:italic>P. gingivalis</ce:italic> , GF and PDLF demonstrate different profiles of IL-6 and PGE2 production. IL-6 production is stimulated in GF by LPS from <ce:italic>P. gingivalis, Actinobacillus actinomycetemcomitans and Salmonella enteritidis</ce:italic> <ce:cross-ref refid="bib9"><ce:sup>9</ce:sup></ce:cross-ref> and in PDLF by interleukin-1β. <ce:cross-ref refid="bib30"><ce:sup>30</ce:sup></ce:cross-ref> In this study, however, constitutive GF IL-6 production essentially remained unchanged, which indicated that GF were unresponsive to the tested levels of <ce:italic>P. gingivalis</ce:italic> LPS. In contrast, PDLF produced lower levels of IL-6 constitutively but appeared sensitive to LPS stimulation.</ce:para><ce:para>Because quantification of IL-6 levels within periodontal tissues has not been reported, the clinical significance of the secreted levels of IL-6 from this in vitro study is difficult to interpret. However, data regarding IL-6 levels in GCF collected from diseased and healthy sites have been presented. Geivelis et al. <ce:cross-ref refid="bib20"><ce:sup>20</ce:sup></ce:cross-ref> reported elevated IL-6 levels in GCF taken from diseased sites and demonstrated a strong correlation with bleeding index ( <ce:italic>p</ce:italic> < 0.005) and probing depth ( <ce:italic>p</ce:italic> < 0.05). Reinhardt et al. <ce:cross-ref refid="bib19"><ce:sup>19</ce:sup></ce:cross-ref> also showed that GCF IL-6 levels are increased in refractory periodontitis sites (active disease) compared with stable sites (no active disease). However, PDLF are but one potential source of IL-6 measured in GCF, and other cell types, including GF, are likely secretors. <ce:cross-refs refid="bib11 bib12 bib13"><ce:sup>11-13</ce:sup></ce:cross-refs> Although the quantity of LPS-stimulated IL-6 secretion by the two cell populations was similar, the qualitative nature of the response may be important. The increased IL-6 secreted by PDLF into periodontal connective tissue may be sufficient to precipitate a shift of metabolic homeostasis at the level of crestal bone toward net bone resorption through increased recruitment of osteoclasts or decreased production of collagen by osteoblasts. <ce:cross-refs refid="bib17 bib18 bib44 bib45 bib46"><ce:sup>17,18,44-46</ce:sup></ce:cross-refs></ce:para><ce:para>Both GF and PDLF demonstrated a significant dose- and time-dependent increase in PGE2 production, with PDLF producing higher levels (approximately 11,600 pg/ng DNA/ml in supernatant 72 hours after LPS stimulation). Correlation of PGE2 with clinical periodontal disease exhibits a strong direct relation; numerous studies have demonstrated elevated PGE2 levels in disease tissue compared with healthy tissue. <ce:cross-refs refid="bib47 bib48 bib49 bib50 bib51"><ce:sup>47-51</ce:sup></ce:cross-refs> Again, the effect of increased PGE2, a mediator of bone loss, at the level of crestal bone and in the periodontal ligament may also cause a shift of the bone remodeling process toward net bone resorption.</ce:para><ce:para>Speculating that the more sensitive response of PDLF to LPS stimulation is associated with the resistance to loss of marginal bone height observed around titanium dental implants is tempting, <ce:cross-refs refid="bib52 bib53 bib54"><ce:sup>52-54</ce:sup></ce:cross-refs> despite a periimplant microflora similar to that observed in periodontal sulci. <ce:cross-refs refid="bib55 bib56 bib57"><ce:sup>55-57</ce:sup></ce:cross-refs> Although one proposed criterion of a successful implant is that 0.2 mm/year of marginal bone loss is acceptable after the first year of up to 1 mm of bone loss, <ce:cross-ref refid="bib58"><ce:sup>58</ce:sup></ce:cross-ref> quantitative long-term data comparing bone loss around teeth and implants are limited.</ce:para><ce:para>Van Steenberghe <ce:cross-ref refid="bib53"><ce:sup>53</ce:sup></ce:cross-ref> monitored 558 Brånemark implants inserted in 159 partially edentulous patients over a period of three years and observed that periimplant pocket depths initially decreased and then remained stable. In contrast, periodontal pocket depths significantly increased during the final year of observation, suggesting that the natural dentition was more prone to increases in pocket depth than titanium implants. Taylor, <ce:cross-ref refid="bib59"><ce:sup>59</ce:sup></ce:cross-ref> commenting on clinical data indicating that osseointegrated endosseous dental implants and natural teeth are dissimilar entities, emphasized periimplant inflammation as one such indicator and stated that “To assume that the interface between an osseointegrated implant and surrounding tissues is vulnerable or even susceptible to the same disease process is, perhaps, the ultimate dental assumption.” Additionally, our data appear to lend support to the hypothesis proposed by Zarb and Albrektsson <ce:cross-ref refid="bib60"><ce:sup>60</ce:sup></ce:cross-ref> that the absence of PDL around osseointegrated titanium dental implants may contribute to the observed resistance to loss of marginal bone height. Absence of the PDL around an osseointegrated endosseous implant may be a serendipitous occurrence because of the subsequent lack of PDLF in close proximity to the periosteum of crestal bone that may secrete IL-6 and PGE2 when stimulated with a periodontitis-associated virulence factor. However, confirmation of this hypothesis requires further research, namely comparison of in vivo IL-6 and PGE2 levels at diseased and healthy crestal periodontal and periimplant bone. Anatomic differences between osseointegrated titanium implants and teeth are not limited to the absence or presence of a PDL. <ce:cross-refs refid="bib61 bib62"><ce:sup>61,62</ce:sup></ce:cross-refs> Other differences, such as the structure of the gingival attachment and surrounding connective tissue, may influence the nature of the physiologic response to bacterial virulence factors.</ce:para><ce:para>Despite the majority of the dental fibroblast literature representing biopsy protocols similar to those described for this study, namely a small number of subjects, our results should be interpreted with caution. Future research may identify the presence of subpopulations within GF and PDLF and permit study of the cellular and molecular mechanisms of inflammatory mediator production by GF and PDLF.</ce:para></ce:section><ce:section><ce:section-title>CONCLUSIONS</ce:section-title><ce:para>Within the limitations of the study, the following conclusions were drawn:
<ce:list><ce:list-item><ce:label>1.</ce:label><ce:para>Human PDLF respond to <ce:italic>P. gingivalis</ce:italic> LPS stimulation with increased IL-6 production, whereas GF IL-6 production does not increase above constitutive levels.</ce:para></ce:list-item><ce:list-item><ce:label>2.</ce:label><ce:para>Both PDLF and GF respond to <ce:italic>P. gingivalis</ce:italic> LPS stimulation with elevated PGE2 secretion into culture supernatants. 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Implants</sb:maintitle></sb:title><sb:volume-nr>10</sb:volume-nr></sb:series><sb:date>1995</sb:date></sb:issue><sb:pages><sb:first-page>750</sb:first-page><sb:last-page>758</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference></ce:bibliography-sec></ce:bibliography></tail></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Periodontal pathogen-related stimulation indicates unique phenotype of primary cultured human fibroblasts from gingiva and periodontal ligament: Implications for oral health disease</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Periodontal pathogen-related stimulation indicates unique phenotype of primary cultured human fibroblasts from gingiva and periodontal ligament: Implications for oral health disease</title></titleInfo><name type="personal"><namePart type="given">Sreenivas</namePart><namePart type="family">Koka</namePart><namePart type="termsOfAddress">DDS, MSa</namePart><affiliation>College of Dentistry, University of Nebraska Medical Center, Lincoln, Neb</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Richard A.</namePart><namePart type="family">Reinhardt</namePart><namePart type="termsOfAddress">DDS, MS, PhDb</namePart><affiliation>College of Dentistry, University of Nebraska Medical Center, Lincoln, Neb</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1997</dateIssued><copyrightDate encoding="w3cdtf">1997</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Abstract: Statement of Problem. The fibroblast is considered an important cellular component in periodontitis because it is the predominant cell type in periodontal connective tissue. Purpose. The purpose of this study was to test whether gingival fibroblasts (GF) and periodontal ligament fibroblasts (PDLF) are heterogeneous in their production of inflammatory mediators associated with bone resorption in response to lipopolysaccharides from the gram-negative bacterium Porphyromonas gingivalis . To test this hypothesis, we (1) compared interleukin-6 production by cultured human PDLF and GF isolated from the same individual when exposed to P. gingivalis lipopolysaccharide; and (2) compared prostaglandin-E 2 production by cultured human PDLF and GF isolated from the same individual when exposed to P. gingivalis lipopolysaccharide. Material and Methods. Human periodontal ligament and gingival fibroblasts were cultured from biopsies and exposed to P. gingivalis lipopolysaccharide. Levels of interleukin-6 and prostaglandin-E 2 secreted into culture supernatant were measured by enzyme-linked immunosorbent assay and the data analyzed. Gingival fibroblasts secreted similar interleukin-6 and elevated prostaglandin-E 2 levels compared with unstimulated cells. Periodontal ligament fibroblasts secreted elevated levels of both mediators compared with unstimulated cells. Secreted levels of interleukin-6 and prostaglandin-E 2 by primary gingival and periodontal ligament fibroblast cultures appear to differ when stimulated with a periodontal pathogen-related virulence factor. Conclusion. The fibroblast of the periodontal ligament and the fibroblast of the gingiva may represent different phenotypes that play unique roles in tissue responses to implants. (J Prosthet Dent 1997:77:191-6.)</abstract><note>a Assistant Professor, Immunoregulation Laboratories.</note><note>b Bernard and Ann Moran Professor of Periodontics, Immunoregulation Laboratories.</note><note>Reprint requests to: Dr. Sreenivas Koka Immunoregulation Laboratories College of Dentistry University of Nebraska Medical Center 40th and Holdrege Streets Lincoln, NE 68583-0740</note><note>0022-3913/97/$5.00 + 0 10/1/79110</note><relatedItem type="host"><titleInfo><title>The Journal of Prosthetic Dentistry</title></titleInfo><titleInfo type="abbreviated"><title>YMPR</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">199702</dateIssued></originInfo><identifier type="ISSN">0022-3913</identifier><identifier type="PII">S0022-3913(05)X7037-8</identifier><part><date>199702</date><detail type="volume"><number>77</number><caption>vol.</caption></detail><detail type="issue"><number>2</number><caption>no.</caption></detail><extent unit="issue-pages"><start>109</start><end>230</end></extent><extent unit="pages"><start>191</start><end>196</end></extent></part></relatedItem><identifier type="istex">12FF7F22DDAAB652B59E60A7DE1E00D065964F4C</identifier><identifier type="ark">ark:/67375/6H6-DF0V9S75-M</identifier><identifier type="DOI">10.1016/S0022-3913(97)70234-8</identifier><identifier type="PII">S0022-3913(97)70234-8</identifier><accessCondition type="use and reproduction" contentType="copyright">©1997 Editorial Council of the Journal of Prosthetic Dentistry</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource><recordOrigin>Editorial Council of the Journal of Prosthetic Dentistry, ©1997</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/document/12FF7F22DDAAB652B59E60A7DE1E00D065964F4C/metadata/json</uri></json:item></metadata></istex></record>Pour manipuler ce document sous Unix (Dilib)
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