title: Decreasing NF-κB expression enhances odontoblastic differentiation and collagen expression in dental pulp stem cells exposed to inflammatory cytokines.
abstract: 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.
authors: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas 75246, United States of America.
authors: Neda S T
authors: NS
authors: Hozhabri
authors: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas 75246, United States of America.
authors: M Douglas
authors: MD
authors: Benson
authors: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas 75246, United States of America.
authors: Michael D
authors: MD
authors: Vu
authors: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas 75246, United States of America.
authors: Rinkesh H
authors: RH
authors: Patel
authors: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas 75246, United States of America.
authors: Rebecca M
authors: RM
authors: Martinez
authors: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas 75246, United States of America.
authors: Fatemeh N
authors: FN
authors: Nakhaie
authors: Center for Excellence in Hip Disorders, Texas Scottish Rite Hospital for Children, Dallas, Texas 75219, United States of America.
authors: Harry K W
authors: HK
authors: Kim
authors: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas 75246, United States of America.
authors: Venu G
authors: VG
authors: Varanasi
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D003782:Dental Pulp / Q000166:cytology*; D005109:Extracellular Matrix / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009804:Odontoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D007976:Leupeptins; D016328:NF-kappa B; D034741:RNA, Small Interfering; D003094:Collagen; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
references: Acta Biomater. 2009 Nov;5(9):3536-47
references: 19497391
references: J Clin Invest. 2001 Jan;107(1):3-6
references: 11134170
references: Arch Med Res. 2002 Sep-Oct;33(5):482-4
references: 12459320
references: J Endod. 2006 Sep;32(9):853-61
references: 16934628
references: J Dent Res. 2005 Nov;84(11):994-8
references: 16246929
references: J Oral Implantol. 2012 Aug;38(4):325-36
references: 22913306
references: J Endovasc Ther. 2000 Dec;7(6):469-78
references: 11194818
references: Zhonghua Kou Qiang Yi Xue Za Zhi. 2011 Jul;46(7):406-11
references: 22041629
references: Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13625-30
references: 11087820
references: J Bone Miner Res. 1997 Dec;12(12):2040-9
references: 9421236
references: Eur J Oral Sci. 2000 Jun;108(3):202-6
references: 10872990
references: Pharmacol Res. 2008 Aug;58(2):137-47
references: 18602009
references: Cytokine. 2003 May;22(3-4):84-8
references: 12849707
references: Blood. 2006 Feb 1;107(3):1156-65
references: 16223780
references: Neuroimmunomodulation. 2004;11(6):376-84
references: 15467353
references: Stem Cell Res Ther. 2010;1(1):5
references: 20504286
references: Acta Biochim Biophys Sin (Shanghai). 2006 May;38(5):318-26
references: 16680372
references: Oral Dis. 2007 Mar;13(2):151-7
references: 17305615
references: J Dent Res. 2009 Apr;88(4):339-44
references: 19407154
references: J Dent Educ. 2003 Jun;67(6):678-89
references: 12856968
references: J Dent Res. 2007 Apr;86(4):363-7
references: 17384033
references: Invest Ophthalmol Vis Sci. 2008 May;49(5):1998-2003
references: 18436832
references: Toxicol In Vitro. 2006 Mar;20(2):248-55
references: 16112536
references: J Biol Chem. 2008 Jul 11;283(28):19359-70
references: 18424784
references: J Clin Invest. 2001 Jan;107(1):7-11
references: 11134171
references: Mater Sci Eng C Mater Biol Appl. 2013 Jul 1;33(5):2757-65
references: 23623093
references: Science. 1996 Nov 1;274(5288):784-7
references: 8864119
references: J Immunol. 1999 Jul 1;163(1):427-33
references: 10384145
references: J Immunol. 2002 Feb 1;168(3):1441-6
references: 11801687
references: Int J Biomater. 2012;2012:915620
references: 22988460
references: Mol Biol Rep. 2008 Sep;35(3):291-8
references: 17530443
references: Trends Immunol. 2004 Jun;25(6):280-8
references: 15145317
references: Biomed Mater Eng. 2008;18(4-5):253-60
references: 19065031
references: Cell. 2002 Apr;109 Suppl:S81-96
references: 11983155
references: Int J Exp Pathol. 2006 Oct;87(5):369-72
references: 16965564
references: Arthritis Rheum. 2000 Apr;43(4):801-11
references: 10765924
references: J Biol Chem. 2005 Apr 29;280(17):17472-9
references: 15728577
references: Osteoarthritis Cartilage. 2006 Apr;14(4):367-76
references: 16376111
references: Arthritis Rheum. 2010 Jul;62(7):2160-9
references: 20506183
references: Ann N Y Acad Sci. 2009 Aug;1171:428-35
references: 19723086