Translational Periodontology
Gingival Transcriptome Patterns During Induction and Resolution of Experimental Gingivitis in Humans
Abstract
Background: To our knowledge, changes in the patterns of whole‐transcriptome gene expression that occur during the induction and resolution of experimental gingivitis in humans were not previously explored using bioinformatic tools.
Methods: Gingival biopsy samples collected from 14 subjects during a 28‐day stent‐induced experimental gingivitis model, followed by treatment, and resolution at days 28 through 35 were analyzed using gene‐expression arrays. Biopsy samples were collected at different sites within each subject at baseline (day 0), at the peak of gingivitis (day 28), and at resolution (day 35) and processed using whole‐transcriptome gene‐expression arrays. Gene‐expression data were analyzed to identify biologic themes and pathways associated with changes in gene‐expression profiles that occur during the induction and resolution of experimental gingivitis using bioinformatic tools.
Results: During disease induction and resolution, the dominant expression pathway was the immune response, with 131 immune response genes significantly up‐ or downregulated during induction, during resolution, or during both at P <0.05. During induction, there was significant transient increase in the expression of inflammatory and oxidative stress mediators, including interleukin (IL)‐1 alpha (IL1A), IL‐1 beta (IL1B), IL8, RANTES, colony stimulating factor 3 (CSF3), and superoxide dismutase 2 (SOD2), and a decreased expression of IP10, interferon inducible T‐cell alpha chemoattractant (ITAC), matrix metalloproteinase 10 (MMP10), and beta 4 defensin (DEFB4). These genes reversed expression patterns upon resolution in parallel with the reversal of gingival inflammation.
Conclusions: A relatively small subset (11.9%) of the immune response genes analyzed by array was transiently activated in response to biofilm overgrowth, suggesting a degree of specificity in the transcriptome‐expression response. The fact that this same subset demonstrates a reversal in expression patterns during clinical resolution implicates these genes as being critical for maintaining tissue homeostasis at the biofilm–gingival interface. In addition to the immune response pathway as the dominant response theme, new candidate genes and pathways were identified as being selectively modulated in experimental gingivitis, including neural processes, epithelial defenses, angiogenesis, and wound healing.
Citing Literature
Number of times cited: 44
- Tiago Taiete, Renato Corrêa Viana Casarin, Karina Gonzales Silvério Ruiz, Francisco Humberto Nociti Jr., Enilson Antônio Sallum and Marcio Zaffalon Casati, Transcriptome of healthy gingival tissue from edentulous sites in patients with a history of generalized aggressive periodontitis, Journal of Periodontology, 89, 1, (93-104), (2018).
- Shinya Murakami, Brian L. Mealey, Angelo Mariotti and Iain L.C. Chapple, Dental plaque–induced gingival conditions, Journal of Clinical Periodontology, 45, S20, (S17-S27), (2018).
- Leonardo Trombelli, Roberto Farina, Cléverson O. Silva and Dimitris N. Tatakis, Plaque‐induced gingivitis: Case definition and diagnostic considerations, Journal of Clinical Periodontology, 45, S20, (S44-S67), (2018).
- Leonardo Trombelli, Roberto Farina, Cléverson O. Silva and Dimitris N. Tatakis, Plaque‐induced gingivitis: Case definition and diagnostic considerations, Journal of Periodontology, 89, S1, (S46-S73), (2018).
- Shinya Murakami, Brian L. Mealey, Angelo Mariotti and Iain L.C. Chapple, Dental plaque–induced gingival conditions, Journal of Periodontology, 89, S1, (S17-S27), (2018).
- G. Ramage, D. F. Lappin, E. Millhouse, J. Malcolm, A. Jose, J. Yang, D. J. Bradshaw, J. R. Pratten and S. Culshaw, The epithelial cell response to health and disease associated oral biofilm models, Journal of Periodontal Research, 52, 3, (325-333), (2016).
- D. C. Peruzzo, J. H. Gimenes, T. Taiete, R. C. V. Casarin, M. Feres, E. A. Sallum, M. Z. Casati, K. R. Kantovitz and F. H. Nociti, Impact of smoking on experimental gingivitis. A clinical, microbiological and immunological prospective study, Journal of Periodontal Research, 51, 6, (800-811), (2016).
- Sandra Mazzoli, Biofilm, Compendium of Inflammatory Diseases, 10.1007/978-3-7643-8550-7_82, (215-229), (2016).
- Hubertine ME Willems, Zhenbo Xu and Brian M Peters, Polymicrobial Biofilm Studies: from Basic Science to Biofilm Control, Current Oral Health Reports, 10.1007/s40496-016-0078-y, 3, 1, (36-44), (2016).
- Steven Offenbacher, Kimon Divaris, Silvana P. Barros, Kevin L. Moss, Julie T. Marchesan, Thiago Morelli, Shaoping Zhang, Steven Kim, Lu Sun, James D. Beck, Matthias Laudes, Matthias Munz, Arne S. Schaefer and Kari E. North, Genome-wide association study of biologically informed periodontal complex traits offers novel insights into the genetic basis of periodontal disease, Human Molecular Genetics, 25, 10, (2113), (2016).
- S. Zhang, K. Divaris, K. Moss, N. Yu, S. Barros, J. Marchesan, T. Morelli, C. Agler, S.J. Kim, D. Wu, K.E. North, J. Beck and S. Offenbacher, The Novel ASIC2 Locus Is Associated with Severe Gingival Inflammation, JDR Clinical & Translational Research, 1, 2, (163), (2016).
- Chun-Teh Lee, Ricardo Teles, Alpdogan Kantarci, Tsute Chen, Jon McCafferty, Jacqueline R. Starr, Luciana Carla Neves Brito, Bruce J. Paster and Thomas E. Van Dyke, Resolvin E1 Reverses Experimental Periodontitis and Dysbiosis, The Journal of Immunology, 197, 7, (2796), (2016).
- Paola Carvajal, Mariel Gómez, Sabrina Gomes, Ricardo Costa, Andres Toledo, Fernando Solanes, Hugo Romanelli, Rui Oppermann, Cassiano Rösing and Jorge Gamonal, Prevalence, severity, and risk indicators of gingival inflammation in a multi-center study on South American adults: a cross sectional study, Journal of Applied Oral Science, 24, 5, (524), (2016).
- H. Dommisch, I. Staufenbiel, K. Schulze, M. Stiesch, A. Winkel, R. Fimmers, J. Dommisch, S. Jepsen, N. Miosge, K. Adam and J. Eberhard, Expression of antimicrobial peptides and interleukin‐8 during early stages of inflammation: An experimental gingivitis study, Journal of Periodontal Research, 50, 6, (836-845), (2015).
- J.T. Marchesan, T. Morelli, K. Moss, S.P. Barros, M. Ward, W. Jenkins, M.B. Aspiras and S. Offenbacher, Association of Synergistetes and Cyclodipeptides with Periodontitis, Journal of Dental Research, 94, 10, (1425), (2015).
- Radhakrishnan Nagarajan, Craig S. Miller, Dolph Dawson, Mohanad Al-Sabbagh, Jeffrey L. Ebersole and Özlem Yilmaz, Patient-Specific Variations in Biomarkers across Gingivitis and Periodontitis, PLOS ONE, 10, 9, (e0136792), (2015).
- N. Yu, S.P. Barros, S. Zhang, K.L. Moss, S.T. Phillips and S. Offenbacher, Insulin Response Genes in Different Stages of Periodontal Disease, Journal of Dental Research, 94, 9_suppl, (194S), (2015).
- Thiago Morelli, Michael Stella, Silvana P. Barros, Julie T. Marchesan, Kevin L. Moss, Steven J. Kim, Ning Yu, Marcelo B. Aspiras, Marilyn Ward and Steven Offenbacher, Salivary Biomarkers in a Biofilm Overgrowth Model, Journal of Periodontology, 85, 12, (1770-1778), (2014).
- Octavio A. Gonzalez, Michael J. Novak, Sreenatha Kirakodu, Luis Orraca, Kuey‐Chu Chen, Arny Stromberg, Janis Gonzalez‐Martinez and Jeffrey L. Ebersole, Comparative analysis of gingival tissue antigen presentation pathways in ageing and periodontitis, Journal of Clinical Periodontology, 41, 4, (327-339), (2014).
- Mayank Hans and Veenu Madaan Hans, Epithelial Antimicrobial Peptides: Guardian of the Oral Cavity, International Journal of Peptides, 2014, (1), (2014).
- Leila S. Coimbra, Joao Paulo Steffens, Carlos Rossa, Dana T. Graves and Luis C. Spolidorio, Clopidogrel enhances periodontal repair in rats through decreased inflammation, Journal of Clinical Periodontology, 41, 3, (295-302), (2014).
- Shi Huang, Rui Li, Xiaowei Zeng, Tao He, Helen Zhao, Alice Chang, Cunpei Bo, Jie Chen, Fang Yang, Rob Knight, Jiquan Liu, Catherine Davis and Jian Xu, Predictive modeling of gingivitis severity and susceptibility via oral microbiota, The ISME Journal, 8, 9, (1768), (2014).
- Emma Millhouse, Anto Jose, Leighann Sherry, David F Lappin, Nisha Patel, Andrew M Middleton, Jonathan Pratten, Shauna Culshaw and Gordon Ramage, Development of an in vitroperiodontal biofilm model for assessing antimicrobial and host modulatory effects of bioactive molecules, BMC Oral Health, 14, 1, (2014).
- Ricardo Teles, Flavia Teles, Jorge Frias‐Lopez, Bruce Paster and Anne Haffajee, Lessons learned and unlearned in periodontal microbiology, Periodontology 2000, 62, 1, (95-162), (2013).
- I Glurich, A Acharya, SK Shukla, GR Nycz and MH Brilliant, The oral‐systemic personalized medicine model at Marshfield Clinic, Oral Diseases, 19, 1, (1-17), (2012).
- Nagihan Bostanci, Per Ramberg, Åsa Wahlander, Jonas Grossman, Daniel Jönsson, Virginia Monsul Barnes and Panos N. Papapanou, Label-Free Quantitative Proteomics Reveals Differentially Regulated Proteins in Experimental Gingivitis, Journal of Proteome Research, 10.1021/pr300761e, 12, 2, (657-678), (2013).
- K. Divaris, K. L. Monda, K. E. North, A. F. Olshan, L. M. Reynolds, W.-C. Hsueh, E. M. Lange, K. Moss, S. P. Barros, R. J. Weyant, Y. Liu, A. B. Newman, J. D. Beck and S. Offenbacher, Exploring the genetic basis of chronic periodontitis: a genome-wide association study, Human Molecular Genetics, 10.1093/hmg/ddt065, 22, 11, (2312-2324), (2013).
- B.G. Loos and G. Papantonopoulos, Molecular Biotypes for Periodontal Diseases?, Journal of Dental Research, 92, 12, (1056), (2013).
- M. M. Grant, What do ’omic technologies have to offer periodontal clinical practice in the future?, Journal of Periodontal Research, 47, 1, (2-14), (2011).
- Angie Lee, Carrie B. Ghaname, Thomas M. Braun, James V. Sugai, Ricardo P. Teles, Walter J. Loesche, Kenneth S. Kornman, William V. Giannobile and Janet S. Kinney, Bacterial and Salivary Biomarkers Predict the Gingival Inflammatory Profile, Journal of Periodontology, 83, 1, (79-89), (2012).
- O.M. Andriankaja, J. Galicia, G. Dong, W. Xiao, F. Alawi and D.T. Graves, Gene Expression Dynamics during Diabetic Periodontitis, Journal of Dental Research, 10.1177/0022034512465292, 91, 12, (1160-1165), (2012).
- B S Sorenson, A Khammanivong, B D Guenther, K F Ross and M C Herzberg, IL-1 receptor regulates S100A8/A9-dependent keratinocyte resistance to bacterial invasion, Mucosal Immunology, 5, 1, (66), (2012).
- Ulvi Kahraman Gursoy and Eija Könönen, Understanding the roles of gingival beta-defensins, Journal of Oral Microbiology, 4, 1, (15127), (2012).
- Janaina Salomon Ghizoni, Luís Antônio de Assis Taveira, Gustavo Pompermaier Garlet, Marcos Flávio Ghizoni, Jefferson Ricardo Pereira, Thiago José Dionísio, Daniel Thomas Brozoski, Carlos Ferreira Santos and Adriana Campos Passanezi Sant'Ana, Increased levels of Porphyromonas gingivalis are associated with ischemic and hemorrhagic cerebrovascular disease in humans: an in vivo study, Journal of Applied Oral Science, 20, 1, (104), (2012).
- Ann E. Scott, Mike Milward, Gerard J. Linden, John B. Matthews, Monica J. Carlile, Fionnuala T. Lundy, Mojgan A. Naeeni, S. Lorraine Martin, Brian Walker, Denis Kinane, Gareth R. Brock and Iain L. C. Chapple, Mapping biological to clinical phenotypes during the development (21 days) and resolution (21 days) of experimental gingivitis, Journal of Clinical Periodontology, 39, 2, (123-131), (2011).
- D. Abe, T. Kubota, T. Morozumi, T. Shimizu, N. Nakasone, M. Itagaki and H. Yoshie, Altered gene expression in leukocyte transendothelial migration and cell communication pathways in periodontitis‐affected gingival tissues, Journal of Periodontal Research, 46, 3, (345-353), (2011).
- V. Bakthavatchalu, A. Meka, J.J. Mans, S. Sathishkumar, M.C. Lopez, I. Bhattacharyya, B.F. Boyce, H.V. Baker, R.J. Lamont, J.L. Ebersole and L. Kesavalu, Polymicrobial periodontal pathogen transcriptomes in calvarial bone and soft tissue, Molecular Oral Microbiology, 26, 5, (303-320), (2011).
- G Diamond and LK Ryan, Beta‐defensins: what are they REALLY doing in the oral cavity?, Oral Diseases, 17, 7, (628-635), (2011).
- Shi Huang, Fang Yang, Xiaowei Zeng, Jie Chen, Rui Li, Ting Wen, Chun Li, Wei Wei, Jiquan Liu, Lan Chen, Catherine Davis and Jian Xu, Preliminary characterization of the oral microbiota of Chinese adults with and without gingivitis, BMC Oral Health, 11, 1, (2011).
- Philip M. Preshaw and John J. Taylor, How has research into cytokine interactions and their role in driving immune responses impacted our understanding of periodontitis?, Journal of Clinical Periodontology, 38, (60-84), (2011).
- Daniel Jönsson, Per Ramberg, Ryan T. Demmer, Moritz Kebschull, Gunnar Dahlén and Panos N. Papapanou, Gingival tissue transcriptomes in experimental gingivitis, Journal of Clinical Periodontology, 38, 7, (599-611), (2011).
- Taro Shimizu, Takehiko Kubota, Naohiro Nakasone, Daisuke Abe, Toshiya Morozumi and Hiromasa Yoshie, Microarray and quantitative RT-PCR analyses in calcium-channel blockers induced gingival overgrowth tissues of periodontitis patients, Archives of Oral Biology, 56, 3, (277), (2011).
- V. Bakthavatchalu, A. Meka, S. Sathishkumar, M.C. Lopez, I. Bhattacharyya, B.F. Boyce, J.J. Mans, R.J. Lamont, H.V. Baker, J.L. Ebersole and L. Kesavalu, Tannerella forsythia infection‐induced calvarial bone and soft tissue transcriptional profiles, Molecular Oral Microbiology, 25, 5, (317-330), (2010).
- Jeffrey L. Ebersole, Radhakrishnan Nagarajan, David Akers and Craig S. Miller, Targeted salivary biomarkers for discrimination of periodontal health and disease(s), Frontiers in Cellular and Infection Microbiology, 10.3389/fcimb.2015.00062, 5, (2015).
