Decreasing NF-κB expression enhances odontoblastic differentiation and collagen expression in dental pulp stem cells exposed to inflammatory cytokines
Inflammatory response in the dental pulp can alter the collagen matrix formation by dental pulp stem cells and lead to a delay or poor healing of the pulp. This inflammatory response is mediated by cytokines, including interleukin-1β and tumor necrosis factor-α. In this study, it is hypothesized tha...
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description | Inflammatory response in the dental pulp can alter the collagen matrix formation by dental pulp stem cells and lead to a delay or poor healing of the pulp. This inflammatory response is mediated by cytokines, including interleukin-1β and tumor necrosis factor-α. In this study, it is hypothesized that suppressing the actions of these inflammatory cytokines by knocking down the activity of transcription factor Nuclear Factor-κB will lead to dental pulp stem cell differentiation into odontoblasts and the production of collagen. Here, the role of Nuclear Factor-κB signaling and its reduction was examined during odontogenic behavior in the presence of these cytokines. The results showed a significant increase in Nuclear Factor-κB gene expression and p65 protein expression by interleukin-1β and tumor necrosis factor-α. Nuclear Factor-κB activation in the presence of these cytokines decreased significantly in a dose-dependent manner by a Nuclear Factor-κB inhibitor (MG132) and p65 siRNA. Down-regulation of Nuclear Factor-κB activity also enhanced the gene expression of the odontoblastic markers (dentin sialophosphoprotein, Nestin, and alkaline phosphatase) and displayed an odontoblastic cell morphology indicating the promotion of odontogenic differentiation of dental pulp stem cells. Finally, dental pulp stem cells exposed to reduced Nuclear Factor-κB activity resulted in a significant increase in collagen (I)-α1 expression in the presence of these cytokines. In conclusion, a decrease in Nuclear Factor-κB in dental pulp stem cells in the presence of inflammatory cytokines enhanced odontoblastic differentiation and collagen matrix formation. |
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This inflammatory response is mediated by cytokines, including interleukin-1β and tumor necrosis factor-α. In this study, it is hypothesized that suppressing the actions of these inflammatory cytokines by knocking down the activity of transcription factor Nuclear Factor-κB will lead to dental pulp stem cell differentiation into odontoblasts and the production of collagen. Here, the role of Nuclear Factor-κB signaling and its reduction was examined during odontogenic behavior in the presence of these cytokines. The results showed a significant increase in Nuclear Factor-κB gene expression and p65 protein expression by interleukin-1β and tumor necrosis factor-α. Nuclear Factor-κB activation in the presence of these cytokines decreased significantly in a dose-dependent manner by a Nuclear Factor-κB inhibitor (MG132) and p65 siRNA. Down-regulation of Nuclear Factor-κB activity also enhanced the gene expression of the odontoblastic markers (dentin sialophosphoprotein, Nestin, and alkaline phosphatase) and displayed an odontoblastic cell morphology indicating the promotion of odontogenic differentiation of dental pulp stem cells. Finally, dental pulp stem cells exposed to reduced Nuclear Factor-κB activity resulted in a significant increase in collagen (I)-α1 expression in the presence of these cytokines. In conclusion, a decrease in Nuclear Factor-κB in dental pulp stem cells in the presence of inflammatory cytokines enhanced odontoblastic differentiation and collagen matrix formation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0113334</identifier><identifier>PMID: 25629155</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alkaline phosphatase ; Cell differentiation ; Cell Differentiation - drug effects ; Cell Differentiation - genetics ; Cell morphology ; Cells, Cultured ; Collagen ; Collagen - genetics ; Collagen - metabolism ; Cytokines ; Cytokines - pharmacology ; Cytology ; Dental materials ; Dental pulp ; Dental Pulp - cytology ; Dentin ; Dentistry ; Differentiation (biology) ; Dspp protein ; Extracellular matrix ; Extracellular Matrix - metabolism ; Fibroblasts ; Gene Expression ; Gene Knockdown Techniques ; Humans ; Inflammation ; Inflammation Mediators - pharmacology ; Inflammatory response ; Interleukins ; Kinases ; Leupeptins - pharmacology ; Mesenchymal Stem Cells - cytology ; Mesenchymal Stem Cells - drug effects ; Mesenchymal Stem Cells - metabolism ; Nestin ; NF-kappa B - genetics ; NF-kappa B - metabolism ; NF-κB protein ; Odontoblasts ; Odontoblasts - cytology ; Odontoblasts - drug effects ; Odontoblasts - metabolism ; Rheumatoid arthritis ; RNA Interference ; RNA, Small Interfering - genetics ; Signaling ; siRNA ; Stem cells ; Stem Cells - cytology ; Stem Cells - drug effects ; Stem Cells - metabolism ; Synaptotagmin ; Tissue engineering ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α</subject><ispartof>PloS one, 2015, Vol.10 (1), p.e0113334-e0113334</ispartof><rights>2015 Hozhabri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Hozhabri et al 2015 Hozhabri et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-8fdd270fb60f9a9e00b5064c0aed6665e7e28155273c70942be1a8df49f30ee03</citedby><cites>FETCH-LOGICAL-c526t-8fdd270fb60f9a9e00b5064c0aed6665e7e28155273c70942be1a8df49f30ee03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309458/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309458/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,4010,23845,27900,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25629155$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hozhabri, Neda S T</creatorcontrib><creatorcontrib>Benson, M Douglas</creatorcontrib><creatorcontrib>Vu, Michael D</creatorcontrib><creatorcontrib>Patel, Rinkesh H</creatorcontrib><creatorcontrib>Martinez, Rebecca M</creatorcontrib><creatorcontrib>Nakhaie, Fatemeh N</creatorcontrib><creatorcontrib>Kim, Harry K W</creatorcontrib><creatorcontrib>Varanasi, Venu G</creatorcontrib><title>Decreasing NF-κB expression enhances odontoblastic differentiation and collagen expression in dental pulp stem cells exposed to inflammatory cytokines</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Inflammatory response in the dental pulp can alter the collagen matrix formation by dental pulp stem cells and lead to a delay or poor healing of the pulp. This inflammatory response is mediated by cytokines, including interleukin-1β and tumor necrosis factor-α. In this study, it is hypothesized that suppressing the actions of these inflammatory cytokines by knocking down the activity of transcription factor Nuclear Factor-κB will lead to dental pulp stem cell differentiation into odontoblasts and the production of collagen. Here, the role of Nuclear Factor-κB signaling and its reduction was examined during odontogenic behavior in the presence of these cytokines. The results showed a significant increase in Nuclear Factor-κB gene expression and p65 protein expression by interleukin-1β and tumor necrosis factor-α. Nuclear Factor-κB activation in the presence of these cytokines decreased significantly in a dose-dependent manner by a Nuclear Factor-κB inhibitor (MG132) and p65 siRNA. Down-regulation of Nuclear Factor-κB activity also enhanced the gene expression of the odontoblastic markers (dentin sialophosphoprotein, Nestin, and alkaline phosphatase) and displayed an odontoblastic cell morphology indicating the promotion of odontogenic differentiation of dental pulp stem cells. Finally, dental pulp stem cells exposed to reduced Nuclear Factor-κB activity resulted in a significant increase in collagen (I)-α1 expression in the presence of these cytokines. In conclusion, a decrease in Nuclear Factor-κB in dental pulp stem cells in the presence of inflammatory cytokines enhanced odontoblastic differentiation and collagen matrix formation.</description><subject>Alkaline phosphatase</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Differentiation - genetics</subject><subject>Cell morphology</subject><subject>Cells, Cultured</subject><subject>Collagen</subject><subject>Collagen - genetics</subject><subject>Collagen - metabolism</subject><subject>Cytokines</subject><subject>Cytokines - pharmacology</subject><subject>Cytology</subject><subject>Dental materials</subject><subject>Dental pulp</subject><subject>Dental Pulp - cytology</subject><subject>Dentin</subject><subject>Dentistry</subject><subject>Differentiation (biology)</subject><subject>Dspp protein</subject><subject>Extracellular matrix</subject><subject>Extracellular Matrix - metabolism</subject><subject>Fibroblasts</subject><subject>Gene Expression</subject><subject>Gene Knockdown Techniques</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammation Mediators - pharmacology</subject><subject>Inflammatory response</subject><subject>Interleukins</subject><subject>Kinases</subject><subject>Leupeptins - pharmacology</subject><subject>Mesenchymal Stem Cells - cytology</subject><subject>Mesenchymal Stem Cells - drug effects</subject><subject>Mesenchymal Stem Cells - metabolism</subject><subject>Nestin</subject><subject>NF-kappa B - genetics</subject><subject>NF-kappa B - metabolism</subject><subject>NF-κB protein</subject><subject>Odontoblasts</subject><subject>Odontoblasts - cytology</subject><subject>Odontoblasts - drug effects</subject><subject>Odontoblasts - metabolism</subject><subject>Rheumatoid arthritis</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering - genetics</subject><subject>Signaling</subject><subject>siRNA</subject><subject>Stem cells</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - drug effects</subject><subject>Stem Cells - metabolism</subject><subject>Synaptotagmin</subject><subject>Tissue engineering</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor necrosis factor-α</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptks1u1DAUhSMEoqXwBggssWGTwf9JNkhQKFSqYANry7GvpxkcO9gZxDwJ78JD8Ex4flpNEStHzneOzz26VfWU4AVhDXm1iusUtF9MMcACE8IY4_eqU9IxWkuK2f2j75PqUc4rjAVrpXxYnVAhaUeEOK1-vQOTQOchLNGni_rP77cIfk4Jch5iQBCudTCQUbQxzLH3Os-DQXZwDhKEedDzFtPBIhO910sIx_IhIFso7dG09hPKM4zIgPd5C8UMFs2xQM7rcdRzTBtkNnP8NgTIj6sHTvsMTw7nWfX14v2X84_11ecPl-dvrmojqJzr1llLG-x6iV2nO8C4F1hygzVYKaWABmhbBqUNMw3uOO2B6NY63jmGATA7q57vfScfszp0mhWRAlNCW9EW4nJP2KhXakrDqNNGRT2o3UVMS6VTacWDArCdkcJ0puUcetwT40zJJhxpKLGieL0-vLbuR7CmlJO0v2N6908YrtUy_lCclfC7MC8PBil-X0Oe1TjkbaU6QFzvclNOOe94QV_8g_5_Or6nTIo5J3C3YQhW2z27UantnqnDnhXZs-NBbkU3i8X-Apft1rU</recordid><startdate>2015</startdate><enddate>2015</enddate><creator>Hozhabri, Neda S T</creator><creator>Benson, M Douglas</creator><creator>Vu, Michael D</creator><creator>Patel, Rinkesh H</creator><creator>Martinez, Rebecca M</creator><creator>Nakhaie, Fatemeh N</creator><creator>Kim, Harry K W</creator><creator>Varanasi, Venu G</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</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>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>2015</creationdate><title>Decreasing NF-κB expression enhances odontoblastic differentiation and collagen expression in dental pulp stem cells exposed to inflammatory cytokines</title><author>Hozhabri, Neda S T ; Benson, M Douglas ; Vu, Michael D ; Patel, Rinkesh H ; Martinez, Rebecca M ; Nakhaie, Fatemeh N ; Kim, Harry K W ; Varanasi, Venu G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-8fdd270fb60f9a9e00b5064c0aed6665e7e28155273c70942be1a8df49f30ee03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Alkaline phosphatase</topic><topic>Cell differentiation</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Differentiation - genetics</topic><topic>Cell morphology</topic><topic>Cells, Cultured</topic><topic>Collagen</topic><topic>Collagen - genetics</topic><topic>Collagen - metabolism</topic><topic>Cytokines</topic><topic>Cytokines - pharmacology</topic><topic>Cytology</topic><topic>Dental materials</topic><topic>Dental pulp</topic><topic>Dental Pulp - cytology</topic><topic>Dentin</topic><topic>Dentistry</topic><topic>Differentiation (biology)</topic><topic>Dspp protein</topic><topic>Extracellular matrix</topic><topic>Extracellular Matrix - metabolism</topic><topic>Fibroblasts</topic><topic>Gene Expression</topic><topic>Gene Knockdown Techniques</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Inflammation Mediators - pharmacology</topic><topic>Inflammatory response</topic><topic>Interleukins</topic><topic>Kinases</topic><topic>Leupeptins - pharmacology</topic><topic>Mesenchymal Stem Cells - cytology</topic><topic>Mesenchymal Stem Cells - drug effects</topic><topic>Mesenchymal Stem Cells - metabolism</topic><topic>Nestin</topic><topic>NF-kappa B - genetics</topic><topic>NF-kappa B - metabolism</topic><topic>NF-κB protein</topic><topic>Odontoblasts</topic><topic>Odontoblasts - cytology</topic><topic>Odontoblasts - drug effects</topic><topic>Odontoblasts - metabolism</topic><topic>Rheumatoid arthritis</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering - genetics</topic><topic>Signaling</topic><topic>siRNA</topic><topic>Stem cells</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - drug effects</topic><topic>Stem Cells - metabolism</topic><topic>Synaptotagmin</topic><topic>Tissue engineering</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumor necrosis factor-α</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hozhabri, Neda S T</creatorcontrib><creatorcontrib>Benson, M Douglas</creatorcontrib><creatorcontrib>Vu, Michael D</creatorcontrib><creatorcontrib>Patel, Rinkesh H</creatorcontrib><creatorcontrib>Martinez, Rebecca M</creatorcontrib><creatorcontrib>Nakhaie, Fatemeh N</creatorcontrib><creatorcontrib>Kim, Harry K W</creatorcontrib><creatorcontrib>Varanasi, Venu G</creatorcontrib><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>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</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 Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</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>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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This inflammatory response is mediated by cytokines, including interleukin-1β and tumor necrosis factor-α. In this study, it is hypothesized that suppressing the actions of these inflammatory cytokines by knocking down the activity of transcription factor Nuclear Factor-κB will lead to dental pulp stem cell differentiation into odontoblasts and the production of collagen. Here, the role of Nuclear Factor-κB signaling and its reduction was examined during odontogenic behavior in the presence of these cytokines. The results showed a significant increase in Nuclear Factor-κB gene expression and p65 protein expression by interleukin-1β and tumor necrosis factor-α. Nuclear Factor-κB activation in the presence of these cytokines decreased significantly in a dose-dependent manner by a Nuclear Factor-κB inhibitor (MG132) and p65 siRNA. Down-regulation of Nuclear Factor-κB activity also enhanced the gene expression of the odontoblastic markers (dentin sialophosphoprotein, Nestin, and alkaline phosphatase) and displayed an odontoblastic cell morphology indicating the promotion of odontogenic differentiation of dental pulp stem cells. Finally, dental pulp stem cells exposed to reduced Nuclear Factor-κB activity resulted in a significant increase in collagen (I)-α1 expression in the presence of these cytokines. In conclusion, a decrease in Nuclear Factor-κB in dental pulp stem cells in the presence of inflammatory cytokines enhanced odontoblastic differentiation and collagen matrix formation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25629155</pmid><doi>10.1371/journal.pone.0113334</doi><oa>free_for_read</oa></addata></record> |
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subjects | Alkaline phosphatase Cell differentiation Cell Differentiation - drug effects Cell Differentiation - genetics Cell morphology Cells, Cultured Collagen Collagen - genetics Collagen - metabolism Cytokines Cytokines - pharmacology Cytology Dental materials Dental pulp Dental Pulp - cytology Dentin Dentistry Differentiation (biology) Dspp protein Extracellular matrix Extracellular Matrix - metabolism Fibroblasts Gene Expression Gene Knockdown Techniques Humans Inflammation Inflammation Mediators - pharmacology Inflammatory response Interleukins Kinases Leupeptins - pharmacology Mesenchymal Stem Cells - cytology Mesenchymal Stem Cells - drug effects Mesenchymal Stem Cells - metabolism Nestin NF-kappa B - genetics NF-kappa B - metabolism NF-κB protein Odontoblasts Odontoblasts - cytology Odontoblasts - drug effects Odontoblasts - metabolism Rheumatoid arthritis RNA Interference RNA, Small Interfering - genetics Signaling siRNA Stem cells Stem Cells - cytology Stem Cells - drug effects Stem Cells - metabolism Synaptotagmin Tissue engineering Tumor necrosis factor-TNF Tumor necrosis factor-α |
title | Decreasing NF-κB expression enhances odontoblastic differentiation and collagen expression in dental pulp stem cells exposed to inflammatory cytokines |
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