Repeated lipopolysaccharide stimulation promotes cellular senescence in human dental pulp stem cells (DPSCs)
Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cell (MSC) characterized by multi-lineage differentiation making it an attractive choice for tissue regeneration. However, before DPSCs can be used for cell-based therapy, we have to understand their biological properties in response to i...
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| Veröffentlicht in: | Cell and tissue research 2014-05, Vol.356 (2), p.369-380 |
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| creator | Feng, Xingmei Feng, Guijuan Xing, Jing Shen, Biyu Tan, Wei Huang, Dan Lu, Xiaohui Tao, Tao Zhang, Jinlong Li, Liren Gu, Zhifeng |
| description | Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cell (MSC) characterized by multi-lineage differentiation making it an attractive choice for tissue regeneration. However, before DPSCs can be used for cell-based therapy, we have to understand their biological properties in response to intrinsic and extrinsic stimuli such as lipopolysaccharide (LPS). DPSCs were therefore stimulated with LPS and senescence was evaluated by senescence-associated β-galactosidase (SA-β-gal) staining, with cell number and cell-cycle arrest being examined by BrdU assay and flow cytometry, respectively. The morphology of DPSCs was characterized by their flat shape, increased size and increased SA-β-gal activity after repeated stimulation (3 or 6 times) with LPS. Reactive oxygen species (ROS) staining showed that the number of ROS-stained cells and the DCFH fluorescent level were higher in the LPS-treated DPSCs compared with those in the untreated DPSCs. Protein and mRNA expression levels of γ-H2A.X and p16ᴵᴺᴷ⁴ᴬ were also increased in DPSCs with repeated LPS stimulation. We found that the LPS bound with Toll-like receptor 4 (TLR4) and that TLR4 signaling accounted for p16ᴵᴺᴷ⁴ᴬ expression. Further results indicated that the senescence of DPSCs stimulated repeatedly with LPS was reversed by p16ᴵᴺᴷ⁴ᴬ short interfering RNA. The DNA damage response and p16ᴵᴺᴷ⁴ᴬ pathways might be the main mediators of DPSC senescence induced by repeated LPS stimulation. Thus, DPSCs tend to undergo senescence after repeated activation, implying that DPSC senescence starts after many inflammatory challenges. Ultimately, these findings should lead to a better understanding of DPSC-based clinical therapy. |
| doi_str_mv | 10.1007/s00441-014-1799-7 |
| format | Article |
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However, before DPSCs can be used for cell-based therapy, we have to understand their biological properties in response to intrinsic and extrinsic stimuli such as lipopolysaccharide (LPS). DPSCs were therefore stimulated with LPS and senescence was evaluated by senescence-associated β-galactosidase (SA-β-gal) staining, with cell number and cell-cycle arrest being examined by BrdU assay and flow cytometry, respectively. The morphology of DPSCs was characterized by their flat shape, increased size and increased SA-β-gal activity after repeated stimulation (3 or 6 times) with LPS. Reactive oxygen species (ROS) staining showed that the number of ROS-stained cells and the DCFH fluorescent level were higher in the LPS-treated DPSCs compared with those in the untreated DPSCs. Protein and mRNA expression levels of γ-H2A.X and p16ᴵᴺᴷ⁴ᴬ were also increased in DPSCs with repeated LPS stimulation. We found that the LPS bound with Toll-like receptor 4 (TLR4) and that TLR4 signaling accounted for p16ᴵᴺᴷ⁴ᴬ expression. Further results indicated that the senescence of DPSCs stimulated repeatedly with LPS was reversed by p16ᴵᴺᴷ⁴ᴬ short interfering RNA. The DNA damage response and p16ᴵᴺᴷ⁴ᴬ pathways might be the main mediators of DPSC senescence induced by repeated LPS stimulation. Thus, DPSCs tend to undergo senescence after repeated activation, implying that DPSC senescence starts after many inflammatory challenges. Ultimately, these findings should lead to a better understanding of DPSC-based clinical therapy.</description><identifier>ISSN: 0302-766X</identifier><identifier>EISSN: 1432-0878</identifier><identifier>DOI: 10.1007/s00441-014-1799-7</identifier><identifier>PMID: 24676500</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Adolescent ; Adult ; Apoptosis ; beta-Galactosidase ; Biomedical and Life Sciences ; Biomedicine ; cell cycle ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Cellular Senescence ; Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis ; Cyclin-Dependent Kinase Inhibitor p16 - genetics ; Cyclin-Dependent Kinase Inhibitor p16 - metabolism ; Dental Pulp - cytology ; DNA damage ; DNA Repair ; flow cytometry ; Gene expression ; Histones - biosynthesis ; Human Genetics ; Humans ; Lipopolysaccharides ; Mesenchymal Stem Cells - cytology ; messenger RNA ; Mitogens ; Molar, Third - cytology ; Molecular Medicine ; Protein Binding ; Proteomics ; reactive oxygen species ; Reactive Oxygen Species - metabolism ; Regular Article ; RNA ; RNA Interference ; RNA, Messenger - biosynthesis ; RNA, Small Interfering ; Senescence ; Signal transduction ; small interfering RNA ; Stem cells ; Teeth ; therapeutics ; tissue repair ; Toll-Like Receptor 4 - metabolism ; tooth pulp ; Young Adult</subject><ispartof>Cell and tissue research, 2014-05, Vol.356 (2), p.369-380</ispartof><rights>Springer-Verlag Berlin Heidelberg 2014</rights><rights>COPYRIGHT 2014 Springer</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c624t-7ff5962ce7c054de03bd819abf65a6d384b2a5e83437942b454c5671373c4f1b3</citedby><cites>FETCH-LOGICAL-c624t-7ff5962ce7c054de03bd819abf65a6d384b2a5e83437942b454c5671373c4f1b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00441-014-1799-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00441-014-1799-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,782,786,27933,27934,41497,42566,51328</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24676500$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Feng, Xingmei</creatorcontrib><creatorcontrib>Feng, Guijuan</creatorcontrib><creatorcontrib>Xing, Jing</creatorcontrib><creatorcontrib>Shen, Biyu</creatorcontrib><creatorcontrib>Tan, Wei</creatorcontrib><creatorcontrib>Huang, Dan</creatorcontrib><creatorcontrib>Lu, Xiaohui</creatorcontrib><creatorcontrib>Tao, Tao</creatorcontrib><creatorcontrib>Zhang, Jinlong</creatorcontrib><creatorcontrib>Li, Liren</creatorcontrib><creatorcontrib>Gu, Zhifeng</creatorcontrib><title>Repeated lipopolysaccharide stimulation promotes cellular senescence in human dental pulp stem cells (DPSCs)</title><title>Cell and tissue research</title><addtitle>Cell Tissue Res</addtitle><addtitle>Cell Tissue Res</addtitle><description>Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cell (MSC) characterized by multi-lineage differentiation making it an attractive choice for tissue regeneration. However, before DPSCs can be used for cell-based therapy, we have to understand their biological properties in response to intrinsic and extrinsic stimuli such as lipopolysaccharide (LPS). DPSCs were therefore stimulated with LPS and senescence was evaluated by senescence-associated β-galactosidase (SA-β-gal) staining, with cell number and cell-cycle arrest being examined by BrdU assay and flow cytometry, respectively. The morphology of DPSCs was characterized by their flat shape, increased size and increased SA-β-gal activity after repeated stimulation (3 or 6 times) with LPS. Reactive oxygen species (ROS) staining showed that the number of ROS-stained cells and the DCFH fluorescent level were higher in the LPS-treated DPSCs compared with those in the untreated DPSCs. Protein and mRNA expression levels of γ-H2A.X and p16ᴵᴺᴷ⁴ᴬ were also increased in DPSCs with repeated LPS stimulation. We found that the LPS bound with Toll-like receptor 4 (TLR4) and that TLR4 signaling accounted for p16ᴵᴺᴷ⁴ᴬ expression. Further results indicated that the senescence of DPSCs stimulated repeatedly with LPS was reversed by p16ᴵᴺᴷ⁴ᴬ short interfering RNA. The DNA damage response and p16ᴵᴺᴷ⁴ᴬ pathways might be the main mediators of DPSC senescence induced by repeated LPS stimulation. Thus, DPSCs tend to undergo senescence after repeated activation, implying that DPSC senescence starts after many inflammatory challenges. Ultimately, these findings should lead to a better understanding of DPSC-based clinical therapy.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Apoptosis</subject><subject>beta-Galactosidase</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>cell cycle</subject><subject>Cell Differentiation</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Cellular Senescence</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - genetics</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - metabolism</subject><subject>Dental Pulp - cytology</subject><subject>DNA damage</subject><subject>DNA Repair</subject><subject>flow cytometry</subject><subject>Gene expression</subject><subject>Histones - biosynthesis</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Lipopolysaccharides</subject><subject>Mesenchymal Stem Cells - cytology</subject><subject>messenger RNA</subject><subject>Mitogens</subject><subject>Molar, Third - cytology</subject><subject>Molecular Medicine</subject><subject>Protein Binding</subject><subject>Proteomics</subject><subject>reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Regular Article</subject><subject>RNA</subject><subject>RNA Interference</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Small Interfering</subject><subject>Senescence</subject><subject>Signal transduction</subject><subject>small interfering RNA</subject><subject>Stem cells</subject><subject>Teeth</subject><subject>therapeutics</subject><subject>tissue repair</subject><subject>Toll-Like Receptor 4 - metabolism</subject><subject>tooth pulp</subject><subject>Young Adult</subject><issn>0302-766X</issn><issn>1432-0878</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</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>eNqNkk2L1TAYhYsoznX0B7jRgiDjomO-0y4v108YUBwH3IU0fXtvhjSpSbuYf29qR7mKqGQRSJ7zcnJyiuIxRucYIfkyIcQYrhBmFZZNU8k7xQYzSipUy_pusUEUkUoK8eWkeJDSNcqgEM394oQwIQVHaFO4TzCCnqArnR3DGNxN0sYcdLQdlGmyw-z0ZIMvxxiGMEEqDTiXD2OZwEMy4A2U1peHedC-7MBP2pXj7MashuE7ncqzVx8vd-nFw-Jer12CR7f7aXH15vXn3bvq4sPb97vtRWUEYVMl-543ghiQBnHWAaJtV-NGt73gWnS0Zi3RHGrKqGwYaRlnhguJqaSG9bilp8XZOjeb_jpDmtRg0-JEewhzUpgzlvOTXP4HSihDWMg6o89-Q6_DHH1-yEIRkb3jI2qvHSjr-zBFbZahakslIphlo5k6_wOVVweDNcFDb_P5L4LnR4IDaDcdUnDz8jdJbQVnOQ5C-b_A44l4BU0MKUXo1RjtoOONwkgt9VJrvVRujVrqpZa0ntxGMLcDdD8VP_qUAbICKV_5PcSjjP4y9ekq6nVQeh9tUleXJAO5sJQ2lNBvtUffow</recordid><startdate>20140501</startdate><enddate>20140501</enddate><creator>Feng, Xingmei</creator><creator>Feng, Guijuan</creator><creator>Xing, Jing</creator><creator>Shen, Biyu</creator><creator>Tan, Wei</creator><creator>Huang, Dan</creator><creator>Lu, Xiaohui</creator><creator>Tao, Tao</creator><creator>Zhang, Jinlong</creator><creator>Li, Liren</creator><creator>Gu, Zhifeng</creator><general>Springer-Verlag</general><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature B.V</general><scope>FBQ</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>7QP</scope><scope>7QR</scope><scope>7RV</scope><scope>7SS</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</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>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>7QO</scope></search><sort><creationdate>20140501</creationdate><title>Repeated lipopolysaccharide stimulation promotes cellular senescence in human dental pulp stem cells (DPSCs)</title><author>Feng, Xingmei ; Feng, Guijuan ; Xing, Jing ; Shen, Biyu ; Tan, Wei ; Huang, Dan ; Lu, Xiaohui ; Tao, Tao ; Zhang, Jinlong ; Li, Liren ; Gu, Zhifeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c624t-7ff5962ce7c054de03bd819abf65a6d384b2a5e83437942b454c5671373c4f1b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Apoptosis</topic><topic>beta-Galactosidase</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>cell cycle</topic><topic>Cell Differentiation</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Cellular Senescence</topic><topic>Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis</topic><topic>Cyclin-Dependent Kinase Inhibitor p16 - genetics</topic><topic>Cyclin-Dependent Kinase Inhibitor p16 - metabolism</topic><topic>Dental Pulp - cytology</topic><topic>DNA damage</topic><topic>DNA Repair</topic><topic>flow cytometry</topic><topic>Gene expression</topic><topic>Histones - biosynthesis</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Lipopolysaccharides</topic><topic>Mesenchymal Stem Cells - cytology</topic><topic>messenger RNA</topic><topic>Mitogens</topic><topic>Molar, Third - cytology</topic><topic>Molecular Medicine</topic><topic>Protein Binding</topic><topic>Proteomics</topic><topic>reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Regular Article</topic><topic>RNA</topic><topic>RNA Interference</topic><topic>RNA, Messenger - biosynthesis</topic><topic>RNA, Small Interfering</topic><topic>Senescence</topic><topic>Signal transduction</topic><topic>small interfering RNA</topic><topic>Stem cells</topic><topic>Teeth</topic><topic>therapeutics</topic><topic>tissue repair</topic><topic>Toll-Like Receptor 4 - metabolism</topic><topic>tooth pulp</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Feng, Xingmei</creatorcontrib><creatorcontrib>Feng, Guijuan</creatorcontrib><creatorcontrib>Xing, Jing</creatorcontrib><creatorcontrib>Shen, Biyu</creatorcontrib><creatorcontrib>Tan, Wei</creatorcontrib><creatorcontrib>Huang, Dan</creatorcontrib><creatorcontrib>Lu, Xiaohui</creatorcontrib><creatorcontrib>Tao, Tao</creatorcontrib><creatorcontrib>Zhang, Jinlong</creatorcontrib><creatorcontrib>Li, Liren</creatorcontrib><creatorcontrib>Gu, Zhifeng</creatorcontrib><collection>AGRIS</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>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</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>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>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</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>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><jtitle>Cell and tissue research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Feng, Xingmei</au><au>Feng, Guijuan</au><au>Xing, Jing</au><au>Shen, Biyu</au><au>Tan, Wei</au><au>Huang, Dan</au><au>Lu, Xiaohui</au><au>Tao, Tao</au><au>Zhang, Jinlong</au><au>Li, Liren</au><au>Gu, Zhifeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Repeated lipopolysaccharide stimulation promotes cellular senescence in human dental pulp stem cells (DPSCs)</atitle><jtitle>Cell and tissue research</jtitle><stitle>Cell Tissue Res</stitle><addtitle>Cell Tissue Res</addtitle><date>2014-05-01</date><risdate>2014</risdate><volume>356</volume><issue>2</issue><spage>369</spage><epage>380</epage><pages>369-380</pages><issn>0302-766X</issn><eissn>1432-0878</eissn><abstract>Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cell (MSC) characterized by multi-lineage differentiation making it an attractive choice for tissue regeneration. However, before DPSCs can be used for cell-based therapy, we have to understand their biological properties in response to intrinsic and extrinsic stimuli such as lipopolysaccharide (LPS). DPSCs were therefore stimulated with LPS and senescence was evaluated by senescence-associated β-galactosidase (SA-β-gal) staining, with cell number and cell-cycle arrest being examined by BrdU assay and flow cytometry, respectively. The morphology of DPSCs was characterized by their flat shape, increased size and increased SA-β-gal activity after repeated stimulation (3 or 6 times) with LPS. Reactive oxygen species (ROS) staining showed that the number of ROS-stained cells and the DCFH fluorescent level were higher in the LPS-treated DPSCs compared with those in the untreated DPSCs. Protein and mRNA expression levels of γ-H2A.X and p16ᴵᴺᴷ⁴ᴬ were also increased in DPSCs with repeated LPS stimulation. We found that the LPS bound with Toll-like receptor 4 (TLR4) and that TLR4 signaling accounted for p16ᴵᴺᴷ⁴ᴬ expression. Further results indicated that the senescence of DPSCs stimulated repeatedly with LPS was reversed by p16ᴵᴺᴷ⁴ᴬ short interfering RNA. The DNA damage response and p16ᴵᴺᴷ⁴ᴬ pathways might be the main mediators of DPSC senescence induced by repeated LPS stimulation. Thus, DPSCs tend to undergo senescence after repeated activation, implying that DPSC senescence starts after many inflammatory challenges. Ultimately, these findings should lead to a better understanding of DPSC-based clinical therapy.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>24676500</pmid><doi>10.1007/s00441-014-1799-7</doi><tpages>12</tpages></addata></record> |
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| ispartof | Cell and tissue research, 2014-05, Vol.356 (2), p.369-380 |
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| subjects | Adolescent Adult Apoptosis beta-Galactosidase Biomedical and Life Sciences Biomedicine cell cycle Cell Differentiation Cell Proliferation Cells, Cultured Cellular Senescence Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis Cyclin-Dependent Kinase Inhibitor p16 - genetics Cyclin-Dependent Kinase Inhibitor p16 - metabolism Dental Pulp - cytology DNA damage DNA Repair flow cytometry Gene expression Histones - biosynthesis Human Genetics Humans Lipopolysaccharides Mesenchymal Stem Cells - cytology messenger RNA Mitogens Molar, Third - cytology Molecular Medicine Protein Binding Proteomics reactive oxygen species Reactive Oxygen Species - metabolism Regular Article RNA RNA Interference RNA, Messenger - biosynthesis RNA, Small Interfering Senescence Signal transduction small interfering RNA Stem cells Teeth therapeutics tissue repair Toll-Like Receptor 4 - metabolism tooth pulp Young Adult |
| title | Repeated lipopolysaccharide stimulation promotes cellular senescence in human dental pulp stem cells (DPSCs) |
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