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Chiang CY, Hsu CC, Chen YW, Fu E. Hypomethylation of the interleukin-6 promoter in gingival tissue of patients with periodontitis. J Periodontol 2025. [PMID: 40298280 DOI: 10.1002/jper.24-0698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 02/11/2025] [Accepted: 03/21/2025] [Indexed: 04/30/2025]
Abstract
BACKGROUND DNA methylation may influence cytokine expression and clinical manifestations of periodontitis. This study assessed the interleukin (IL)-6 DNA methylation in gingivae with and without clinical inflammation and its impact on clinical manifestations and cytokine expression. METHODS Sixty-two gingival biopsies (17 from controls and 45 from periodontitis sites) were analyzed. IL-6 protein concentrations were measured using an enzyme-linked immunosorbent assay, and methylation of the IL-6 promoter was analyzed by bisulfite sequencing. At 19 motifs spanning from 1200 to 27 base pairs (bp), the methylation rates for each motif and the overall promoter region were assessed. RESULTS IL-6 concentrations were significantly higher in the periodontitis group than in the control group (135.69 ± 10.24 vs. 65.17 ± 29.18 pg/mL) and were positively correlated with probing depth (PD) and clinical attachment loss (CAL) (r = 0.59 and 0.48, respectively). The overall methylation rate was significantly lower in the disease group (43.97% ± 4.54% vs. 39.54% ± 7.66%) and negatively correlated with PD, CAL, and IL-6 concentrations. Similar trends were also observed for the -74-bp motif: The methylation rate was lower in the periodontitis group than in the control group (8.9% vs. 41.2%, with a relative risk of 0.216), and gingivae with methylation at -74-bp exhibited lower PD and CALs but higher overall methylation rates. CONCLUSION DNA hypomethylation of the IL-6 promoter region, particularly the -74-bp motif, was linked to increased cytokine expression and periodontal clinical signs, suggesting its role in disease progression. PLAIN LANGUAGE SUMMARY This study examined how changes in the interleukin (IL)-6 gene-specifically through a process called DNA methylation-are linked to gum disease (periodontitis) and its symptoms. Sixty-two gum tissue samples were collected: 17 from individuals without gum disease and 45 from those with it. The gum tissues from people with periodontitis showed higher levels of the IL-6 protein, which were associated with more severe gum damage, such as deeper pockets around the teeth and greater loss of attachment. The researchers also found that a part of the IL-6 gene was less methylated in people with gum disease-a change that can lead to increased gene activity. This was especially evident at a specific site in the gene, 74 base pairs from the start. Lower methylation at this site was linked to higher IL-6 levels and more severe symptoms. Overall, the findings suggest that reduced methylation of the IL-6 gene may contribute to the progression of gum disease.
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Affiliation(s)
- Cheng-Yang Chiang
- Institute of Dental Sciences, National Defense Medical Center, Taipei, Taiwan, ROC
- Periodontics Division, Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Cheng-Chieh Hsu
- Institute of Dental Sciences, National Defense Medical Center, Taipei, Taiwan, ROC
- Periodontics Division, Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Ying-Wu Chen
- Institute of Dental Sciences, National Defense Medical Center, Taipei, Taiwan, ROC
- Periodontics Division, Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Earl Fu
- Periodontics Division, Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
- Department of Dentistry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Xindian, New Taipei City, Taiwan, ROC
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Kang J, Yu H, Xiang X, Ma YQ, Zhang L, Zhang Y, Wang ZT, Yang J, Zhang Z, Zou HR, Wang Y. The Histone Demethylase Inhibitor GSK-J4 Attenuates Periodontal Bone Loss and Inflammation in a Rat Model of Periodontitis. Curr Med Sci 2025; 45:382-390. [PMID: 40048054 DOI: 10.1007/s11596-025-00018-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 01/21/2025] [Accepted: 01/26/2025] [Indexed: 04/02/2025]
Abstract
OBJECTIVE To investigate the treatment effect of the histone demethylase inhibitor GSK-J4, a small molecule that inhibits the demethylase activity of Jumonji domain-containing protein 3 (JMJD3), in the treatment of periodontitis. METHODS Gingival tissues from patients with moderate to severe chronic periodontitis and healthy controls were collected to evaluate JMJD3 expression via real-time quantitative reverse transcription PCR (RT-qPCR) and immunohistochemistry (IHC). Next, Sprague-Dawley (SD) rats were used to investigate the effect of GSK-J4 in vivo. The experimental periodontitis model was induced by upper first molar ligation and gingival sulcus injection of Porphyromonas gingivalis. The rats were divided into a healthy group, a periodontitis group, periodontitis plus GSK-J4 treatment groups (P + GSK-J4 15 mg/kg or 25 mg/kg), and a periodontitis plus dimethyl sulfoxide (DMSO) group (P + DMSO). After 4 weeks, maxillary molar segments were assessed via micro-computed tomography (CT) and hematoxylin and eosin (HE) staining. Serum tumor necrosis factor-α (TNF-α) levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS Higher expression of the Jmjd3 gene and JMJD3 protein was detected in human inflamed gingiva than in healthy gingiva (P < 0.05). GSK-J4 administration reversed alveolar bone absorption [i.e., reduced alveolar bone crest (ABC)-cementoenamel junction (CEJ) distance], reduced inflammatory cell accumulation at the crest of the alveolar bone, and alleviated serum TNF-α levels in rats with periodontitis. Moreover, the number of H3K27me3-positive nuclei was greater in model rats treated with GSK J4 than in model rats. CONCLUSIONS The histone demethylase inhibitor GSK-J4 attenuated periodontal bone loss and inflammation in a rat periodontitis model by targeting JMJD3.
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Affiliation(s)
- Jian Kang
- Department of Periodontology, School of Medicine, Tianjin Stomatological Hospital, Nankai University, Tianjin, 300041, China.
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, 300041, China.
| | - Huan Yu
- Department of Periodontology, School of Medicine, Tianjin Stomatological Hospital, Nankai University, Tianjin, 300041, China
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, 300041, China
| | - Xu Xiang
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, 300041, China.
- Department of Oral and Maxillofacial Surgery, School of Medicine, Tianjin Stomatological Hospital, Nankai University, Tianjin, 300041, China.
| | - Yong-Qiang Ma
- Department of Periodontology, School of Medicine, Tianjin Stomatological Hospital, Nankai University, Tianjin, 300041, China
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, 300041, China
| | - Le Zhang
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, 300041, China
- Department of Pathology, School of Medicine, Tianjin Stomatological Hospital, Nankai University, Tianjin, 300041, China
| | - Yuan Zhang
- Department of Periodontology, School of Medicine, Tianjin Stomatological Hospital, Nankai University, Tianjin, 300041, China
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, 300041, China
| | - Zhi-Tao Wang
- Department of Periodontology, School of Medicine, Tianjin Stomatological Hospital, Nankai University, Tianjin, 300041, China
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, 300041, China
| | - Jing Yang
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, 300041, China
- Department of Implantology, School of Medicine, Tianjin Stomatological Hospital, Nankai University, Tianjin, 300041, China
| | - Zheng Zhang
- Department of Periodontology, School of Medicine, Tianjin Stomatological Hospital, Nankai University, Tianjin, 300041, China
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, 300041, China
| | - Hui-Ru Zou
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, 300041, China
- Department of Endodontics, School of Medicine, Tianjin Stomatological Hospital, Nankai University, Tianjin, 300041, China
| | - Yue Wang
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, 300041, China
- School of Medicine, Nankai University, Tianjin, 300071, China
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3
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Zhang J, Liu H, Liu Y, Luo E, Liu S. Unlocking the potential of histone modification in regulating bone metabolism. Biochimie 2024; 227:286-298. [PMID: 39154977 DOI: 10.1016/j.biochi.2024.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 08/02/2024] [Accepted: 08/02/2024] [Indexed: 08/20/2024]
Abstract
Bone metabolism plays a crucial role in maintaining normal bone tissue homeostasis and function. Imbalances between bone formation and resorption can lead to osteoporosis, osteoarthritis, and other bone diseases. The dynamic and complex process of bone remodeling is driven by various factors, including epigenetics. Histone modification, one of the most important and well-studied components of epigenetic regulation, has emerged as a promising area of research in bone metabolism. Different histone proteins and modification sites exert diverse effects on osteogenesis and osteoclastogenesis. In this review, we summarize recent progress in understanding histone modifications in bone metabolism, including specific modification sites and potential regulatory enzymes. Comprehensive knowledge of histone modifications in bone metabolism could reveal new therapeutic targets and treatment strategies for bone diseases.
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Affiliation(s)
- Jiayuan Zhang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Hanghang Liu
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Yao Liu
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - En Luo
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Shibo Liu
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.
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Cores Ziskoven P, Nogueira AVB, Eick S, Deschner J. Apelin Counteracts the Effects of Fusobacterium nucleatum on the Migration of Periodontal Ligament Cells In Vitro. Int J Mol Sci 2024; 25:10729. [PMID: 39409058 PMCID: PMC11476847 DOI: 10.3390/ijms251910729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Revised: 09/30/2024] [Accepted: 10/02/2024] [Indexed: 10/20/2024] Open
Abstract
To better understand the link between periodontitis and metabolic diseases, our in vitro study aimed to assess the influence of the adipokine apelin and/or the periodontal pathogen Fusobacterium nucleatum on periodontal cells. Periodontal ligament (PDL) cells were exposed to F. nucleatum in the presence and absence of apelin. Scratch assays were used to analyze the in vitro wound healing and velocity of cell migration. To investigate if F. nucleatum and/or apelin have a regulatory effect on cell proliferation and apoptosis, proliferation and viability assays were performed as well as an analysis of caspase 9 expression. Both the in vitro wound closure and the cell migration rate were significantly reduced by F. nucleatum. Simultaneous incubation with apelin counteracted the adverse effects of F. nucleatum. The proliferation assay demonstrated that neither apelin nor F. nucleatum significantly affected PDL cell proliferation. Furthermore, neither apelin nor F. nucleatum was cytotoxic or affected apoptosis after 48 h. Apelin could play a modulatory role in the pathogenesis of periodontitis, as it was able to compensate for the inhibitory effects of the periodontal pathogen F. nucleatum on PDL cell migration in vitro.
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Affiliation(s)
- Pablo Cores Ziskoven
- Department of Periodontology and Operative Dentistry, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany; (P.C.Z.); (A.V.B.N.)
| | - Andressa V. B. Nogueira
- Department of Periodontology and Operative Dentistry, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany; (P.C.Z.); (A.V.B.N.)
| | - Sigrun Eick
- Department of Periodontology, School of Dental Medicine, University of Bern, 3010 Bern, Switzerland;
| | - James Deschner
- Department of Periodontology and Operative Dentistry, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany; (P.C.Z.); (A.V.B.N.)
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Khalid S, Kearney M, McReynolds DE. Can social adversity alter the epigenome, trigger oral disease, and affect future generations? Ir J Med Sci 2024; 193:2597-2606. [PMID: 38740675 PMCID: PMC11450135 DOI: 10.1007/s11845-024-03697-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 04/27/2024] [Indexed: 05/16/2024]
Abstract
The nature versus nurture debate has intrigued scientific circles for decades. Although extensive research has established a clear relationship between genetics and disease development, recent evidence has highlighted the insufficiency of attributing adverse health outcomes to genetic factors alone. In fact, it has been suggested that environmental influences, such as socioeconomic position (SEP), may play a much larger role in the development of disease than previously thought, with extensive research suggesting that low SEP is associated with adverse health conditions. In relation to oral health, a higher prevalence of caries (tooth decay) exists among those of low SEP. Although little is known about the biological mechanisms underlying this relationship, epigenetic modifications resulting from environmental influences have been suggested to play an important role. This review explores the intersection of health inequalities and epigenetics, the role of early-life social adversity and its long-term epigenetic impacts, and how those living within the lower hierarchies of the socioeconomic pyramid are indeed at higher risk of developing diseases, particularly in relation to oral health. A deeper understanding of these mechanisms could lead to the development of targeted interventions for individuals of low SEP to improve oral health or identify those who are at higher risk of developing oral disease.
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Affiliation(s)
- Sakr Khalid
- Dublin Dental University Hospital, Trinity College Dublin, Dublin, Ireland
| | - Michaela Kearney
- Dublin Dental University Hospital, Trinity College Dublin, Dublin, Ireland
| | - David E McReynolds
- Dublin Dental University Hospital, Trinity College Dublin, Dublin, Ireland.
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Kim B, Song A, Son A, Shin Y. Gut microbiota and epigenetic choreography: Implications for human health: A review. Medicine (Baltimore) 2024; 103:e39051. [PMID: 39029010 PMCID: PMC11398772 DOI: 10.1097/md.0000000000039051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 07/02/2024] [Indexed: 07/21/2024] Open
Abstract
The interwoven relationship between gut microbiota and the epigenetic landscape constitutes a pivotal axis in understanding human health and disease. Governed by a myriad of dietary, genetic, and environmental influences, the gut microbiota orchestrates a sophisticated metabolic interplay, shaping nutrient utilization, immune responses, and defenses against pathogens. Recent strides in genomics and metabolomics have shed light on the intricate connections between these microbial influencers and the host's physiological dynamics, presenting a dynamic panorama across diverse disease spectra. DNA methylation and histone modifications, as key players in epigenetics, intricately align with the dynamic orchestration of the gut microbiota. This seamless collaboration, notably evident in conditions like inflammatory bowel disease and obesity, has captured the attention of researchers, prompting an exploration of its nuanced choreography. Nevertheless, challenges abound. Analyzing data is intricate due to the multifaceted nature of the gut microbiota and the limitations of current analytical methods. This underscores the need for a multidisciplinary approach, where diverse disciplines converge to pave innovative research pathways. The integration of insights from microbiome and epigenome studies assumes paramount importance in unraveling the complexities of this intricate partnership. Deciphering the synchronized interactions within this collaboration offers a deeper understanding of these delicate interplays, potentially heralding revolutionary strides in treatment modalities and strategies for enhancing public health.
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Affiliation(s)
- Bailee Kim
- Crescenta Valley High School, La Crescenta, CA
| | - Angel Song
- Harvard-Westlake School, Studio City, CA
| | - Andrew Son
- Bellarmine College Preparatory, San Jose, CA
| | - Yonghwan Shin
- Department of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA
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7
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Liaw A, Liu C, Bartold M, Ivanovski S, Han P. Effect of non-surgical periodontal therapy on salivary histone deacetylases expression: A prospective clinical study. J Clin Periodontol 2024; 51:926-935. [PMID: 38468415 DOI: 10.1111/jcpe.13973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 01/31/2024] [Accepted: 02/26/2024] [Indexed: 03/13/2024]
Abstract
AIM To evaluate the effect of non-surgical periodontal therapy (NSPT) on salivary histone deacetylases (HDACs) gene expression in patients with Stage III-IV periodontitis at baseline and at 3 and 6 months post NSPT treatment. MATERIALS AND METHODS Twenty patients completed the study. Periodontitis (as well as the corresponding staging and grading) was diagnosed according to the 2017 World Workshop Classification. Clinical measures were recorded and whole unstimulated saliva was collected at baseline and at 3 and 6 months after NSPT. The expression of 11 HDACs was determined using reverse-transcription PCR, and the respective changes over time were evaluated. RESULTS Six months after NSPT, significant improvements in all clinical periodontal parameters were observed, concomitant with significant up-regulation of HDAC2, 4, 6, 8, 9 and 11 expressions. Subgroup analyses of non-responders and responders revealed no significant differences in HDACs mRNA expression between groups at any time point. CONCLUSIONS This prospective clinical study identified longitudinal changes in salivary HDACs expression in response to NSPT, which provides new insights into the epigenetic mechanisms underlying the pathobiology of periodontitis and creates avenues for the discovery of novel biomarkers.
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Affiliation(s)
- Andrew Liaw
- School of Dentistry, The University of Queensland, Brisbane, Australia
- School of Dentistry, Center for Orofacial Regeneration, Rehabilitation and Reconstruction (COR3), The University of Queensland, Brisbane, Australia
| | - Chun Liu
- School of Dentistry, The University of Queensland, Brisbane, Australia
- School of Dentistry, Center for Orofacial Regeneration, Rehabilitation and Reconstruction (COR3), The University of Queensland, Brisbane, Australia
| | - Mark Bartold
- School of Dentistry, The University of Queensland, Brisbane, Australia
- School of Dentistry, Center for Orofacial Regeneration, Rehabilitation and Reconstruction (COR3), The University of Queensland, Brisbane, Australia
| | - Sašo Ivanovski
- School of Dentistry, The University of Queensland, Brisbane, Australia
- School of Dentistry, Center for Orofacial Regeneration, Rehabilitation and Reconstruction (COR3), The University of Queensland, Brisbane, Australia
| | - Pingping Han
- School of Dentistry, The University of Queensland, Brisbane, Australia
- School of Dentistry, Center for Orofacial Regeneration, Rehabilitation and Reconstruction (COR3), The University of Queensland, Brisbane, Australia
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8
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Wazahat R, Zaidi R, Kumar P. Epigenetic regulations in Mycobacterium tuberculosis infection. Indian J Tuberc 2024; 71:204-212. [PMID: 38589125 DOI: 10.1016/j.ijtb.2023.06.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 06/02/2023] [Accepted: 06/22/2023] [Indexed: 04/10/2024]
Abstract
Mycobacterium tuberculosis (Mtb) employs several sophisticated strategies to evade host immunity and facilitate its intracellular survival. One of them is the epigenetic manipulation of host chromatin by three strategies i.e., DNA methylation, histone modifications and miRNA involvement. A host-directed therapeutic can be an attractive approach that targets these host epigenetics or gene regulations and circumvent manipulation of host cell machinery by Mtb. Given the complexity of the nature of intracellular infection by Mtb, there are challenges in identifying the important host proteins, non-coding RNA or the secretory proteins of Mtb itself that directly or indirectly bring upon the epigenetic modifications in the host chromatin. Equally challenging is developing the methods of targeting these epigenetic factors through chemical or non-chemical approaches as host-directed therapeutics. The current review article briefly summarizes several of the epigenetic factors that serve to bring upon potential changes in the host transcriptional machinery and targets the immune system for immunosuppression and disease progression in Mtb infection.
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Affiliation(s)
- Rushna Wazahat
- Department of Biochemistry, Jamia Hamdard, New Delhi 110062, India.
| | - Rana Zaidi
- Department of Biochemistry, Jamia Hamdard, New Delhi 110062, India
| | - Pankaj Kumar
- Department of Biochemistry, Jamia Hamdard, New Delhi 110062, India.
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Malcangi G, Patano A, Guglielmo M, Sardano R, Palmieri G, Di Pede C, de Ruvo E, Inchingolo AD, Mancini A, Inchingolo F, Bordea IR, Dipalma G, Inchingolo AM. Precision Medicine in Oral Health and Diseases: A Systematic Review. J Pers Med 2023; 13:jpm13050725. [PMID: 37240895 DOI: 10.3390/jpm13050725] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 04/23/2023] [Accepted: 04/24/2023] [Indexed: 05/28/2023] Open
Abstract
Precision medicine (PM) is personalized medicine that can develop targeted medical therapies for the individual patient, in which "omics" sciences lead to an integration of data that leads to highly predictive models of the functioning of the individual biological system. They enable rapid diagnosis, assessment of disease dynamics, identification of targeted treatment protocols, and reduction of costs and psychological stress. "Precision dentistry" (DP) is one promising application that need further investigation; the purpose of this paper is therefore to give physicians an overview of the knowledge they need to enhance treatment planning and patient response to therapy. A systematic literature review was conducted on the PubMed, Scopus, and Web of Science databases by analyzing the articles examining the role of precision medicine in dentistry. PM aims to shed light on cancer prevention strategies, by identifying risk factors, and on malformations such as orofacial cleft. Another application is pain management by repurposing drugs created for other diseases to target biochemical mechanisms. The significant heritability of traits regulating bacterial colonization and local inflammatory responses is another result of genomic research, and is useful for DP in the field of caries and periodontitis. This approach may also be useful in the field of orthodontics and regenerative dentistry. The possibility of creating an international network of databases will lead to the diagnosis, prediction, and prevention of disease outbreaks, providing significant economic savings for the world's health care systems.
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Affiliation(s)
- Giuseppina Malcangi
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70121 Bari, Italy
| | - Assunta Patano
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70121 Bari, Italy
| | | | - Roberta Sardano
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70121 Bari, Italy
| | - Giulia Palmieri
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70121 Bari, Italy
| | - Chiara Di Pede
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70121 Bari, Italy
| | - Elisabetta de Ruvo
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70121 Bari, Italy
| | | | - Antonio Mancini
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70121 Bari, Italy
| | - Francesco Inchingolo
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70121 Bari, Italy
| | - Ioana Roxana Bordea
- Department of Oral Rehabilitation, Faculty of Dentistry, Iuliu Hațieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Gianna Dipalma
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70121 Bari, Italy
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Liaw A, Liu C, Bartold M, Ivanovski S, Han P. Salivary histone deacetylase in periodontal disease: A cross-sectional pilot study. J Periodontal Res 2023; 58:433-443. [PMID: 36717759 DOI: 10.1111/jre.13104] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 01/04/2023] [Accepted: 01/18/2023] [Indexed: 02/01/2023]
Abstract
OBJECTIVE The objective of the study was to profile the expression level of histone deacetylase enzymes (HDACs) in human saliva in periodontal health, gingivitis and periodontitis. BACKGROUND HDACs are epigenetic modulators and a group of enzymes that catalyse the removal of acetyl functional groups from the lysine residues of both histone and nonhistone proteins. HDACs have been detected in gingival tissues and may provide valuable insight into the periodontal inflammatory response. However, no studies have investigated the expression of HDACs in saliva from periodontitis-affected individuals and their capacity for periodontal diagnostics and screening. MATERIALS AND METHODS Whole unstimulated saliva was collected from 53 participants (17 healthy, 14 gingivitis and 22 stages III/IV periodontitis). The expression of 11 HDACs in saliva samples was determined using RT-qPCR and diagnostic power was calculated using the receiver operating characteristic (ROC) curves and area under the ROC Curve (AUC). RESULTS Relative to health, the expression of HDAC4, 8 and 10 was downregulated in gingivitis, and the expression of HDAC4, 6, 8 and 9 was downregulated in periodontitis. Increased HDAC1 and decreased HDAC9 expression were observed in periodontitis compared to gingivitis. Higher HDAC1 and lower HDAC6 and 9 expression was observed in periodontitis compared to non-periodontitis (combining health and gingivitis). Expression of HDAC3, 4, 8, 9 and 10 was significantly decreased in periodontal disease (combining gingivitis and periodontitis) compared to health. HDAC4 and 8 exhibited an excellent diagnostic capacity for distinguishing gingivitis and periodontal disease from health (AUC 0.79-0.86). HDAC9 showed an acceptable power in discriminating periodontitis from health, gingivitis and non-periodontitis (AUC 0.76-0.80). Salivary HDAC enzyme activity showed no significant difference among the groups. CONCLUSION This pilot study has demonstrated the differential expression of HDACs in human saliva for the first time and identified HDAC4, 8 and 9 as potential biomarkers in periodontal diagnosis.
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Affiliation(s)
- Andrew Liaw
- The University of Queensland, School of Dentistry, Brisbane, Queensland, Australia.,The University of Queensland, School of Dentistry, Center for Oral-facial Regeneration, Rehabilitation and Reconstruction (COR3), Brisbane, Queensland, Australia
| | - Chun Liu
- The University of Queensland, School of Dentistry, Brisbane, Queensland, Australia.,The University of Queensland, School of Dentistry, Center for Oral-facial Regeneration, Rehabilitation and Reconstruction (COR3), Brisbane, Queensland, Australia
| | - Mark Bartold
- The University of Queensland, School of Dentistry, Brisbane, Queensland, Australia.,The University of Queensland, School of Dentistry, Center for Oral-facial Regeneration, Rehabilitation and Reconstruction (COR3), Brisbane, Queensland, Australia
| | - Sašo Ivanovski
- The University of Queensland, School of Dentistry, Brisbane, Queensland, Australia.,The University of Queensland, School of Dentistry, Center for Oral-facial Regeneration, Rehabilitation and Reconstruction (COR3), Brisbane, Queensland, Australia
| | - Pingping Han
- The University of Queensland, School of Dentistry, Brisbane, Queensland, Australia.,The University of Queensland, School of Dentistry, Center for Oral-facial Regeneration, Rehabilitation and Reconstruction (COR3), Brisbane, Queensland, Australia
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Bose C, Valentine GC, Philips K, Boggess K, Moss K, Barros SP, Marchesan J, Wu D, O'Shea TM, Peralta-Carcelen M, Goldstein R, Ramamurthy R, Beck JD. Antepartum periodontitis treatment and risk of offspring screening positive for autism spectrum disorder. J Perinatol 2023; 43:470-476. [PMID: 36697694 DOI: 10.1038/s41372-023-01610-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/10/2023] [Accepted: 01/12/2023] [Indexed: 01/26/2023]
Abstract
BACKGROUND To evaluate if treating maternal periodontal disease, a pro-inflammatory condition, during pregnancy (intervention) compared to after pregnancy (control) reduces the likelihood of offspring screening positive for autism spectrum disorder (ASD). METHODS In a follow-up study to the MOTOR randomized trial, we compared rates of positive screens on the Modified Checklist for Autism in Toddlers (M-CHAT) among n = 306 two-year-old toddlers and correlated findings to maternal and cord blood pro-inflammatory interleukin-6 (IL-6). RESULTS Toddlers in the intervention group had decreased risk of a positive M-CHAT screen (adjusted RR = 0.53, 95% CI 0.29-0.99). Toddlers screening positive compared to negative had higher mean IL-6 in cord blood (1.58 ± 1.14 vs. 1.09 ± 0.72 p = 0.001) and maternal IL-6 change from baseline (1.30 ± 0.61 vs 0.96 ± 0.62 p = 0.03). CONCLUSIONS Treating periodontal disease during pregnancy reduced risk of a positive ASD screen. M-CHAT positivity was associated with increased IL-6 in maternal and cord blood. CLINICAL TRIAL Trial Registration numbers: Clinicaltrials.gov NCT03423836.
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Affiliation(s)
- Carl Bose
- Division of Neonatal and Perinatal Medicine, Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Gregory C Valentine
- Division of Neonatology, Department of Pediatrics, University of Washington, Seattle, WA, USA.
| | - Kamaira Philips
- Division of Oral Health and Craniofacial Health Sciences, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA
| | - Kim Boggess
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Kevin Moss
- Division of Oral Health and Craniofacial Health Sciences, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA
| | - Silvana P Barros
- Division of Comprehensive Oral Health, Periodontology Unit, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA
| | - Julie Marchesan
- Division of Comprehensive Oral Health, Periodontology Unit, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA
| | - Di Wu
- Division of Oral Health and Craniofacial Health Sciences, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA
| | - Thomas M O'Shea
- Division of Neonatal and Perinatal Medicine, Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Myriam Peralta-Carcelen
- Department of Pediatrics, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA
| | - Ricki Goldstein
- Division of Neonatology, Department of Pediatrics, Kentucky Children's Hospital, Lexington, KY, USA
| | - Rajam Ramamurthy
- Division of Neonatology, Department of Pediatrics, University of Texas Health Science Center, San Antonio, TX, USA
| | - James D Beck
- Division of Comprehensive Oral Health, Periodontology Unit, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA
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12
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Isola G. Prospective Advances in Genome Editing Investigation. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1396:301-313. [DOI: 10.1007/978-981-19-5642-3_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
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13
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Liaw A, Liu C, Ivanovski S, Han P. The Relevance of DNA Methylation and Histone Modification in Periodontitis: A Scoping Review. Cells 2022; 11:3211. [PMID: 36291079 PMCID: PMC9601099 DOI: 10.3390/cells11203211] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/03/2022] [Accepted: 10/10/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Periodontitis is a chronic inflammatory disease involving an interplay between bacteria, inflammation, host response genes, and environmental factors. The manifestation of epigenetic factors during periodontitis pathogenesis and periodontal inflammation is still not well understood, with limited reviews on histone modification with periodontitis management. This scoping review aims to evaluate current evidence of global and specific DNA methylation and histone modification in periodontitis and discuss the gaps and implications for future research and clinical practice. Methods: A scoping literature search of three electronic databases was performed in SCOPUS, MEDLINE (PubMed) and EMBASE. As epigenetics in periodontitis is an emerging research field, a scoping review was conducted to identify the extent of studies available and describe the overall context and applicability of these results. Results: Overall, 30 studies were evaluated, and the findings confirmed that epigenetic changes in periodontitis comprise specific modifications to DNA methylation patterns and histone proteins modification, which can either dampen or promote the inflammatory response to bacterial challenge. Conclusions: The plasticity of epigenetic modifications has implications for the future development of targeted epi-drugs and diagnostic tools in periodontitis. Such advances could be invaluable for the early detection and monitoring of susceptible individuals.
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Affiliation(s)
- Andrew Liaw
- Center for Oral-facial Regeneration, Rehabilitation and Reconstruction (COR3), The University of Queensland, Brisbane, QLD 4006, Australia
- School of Dentistry, Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, QLD 4006, Australia
| | - Chun Liu
- Center for Oral-facial Regeneration, Rehabilitation and Reconstruction (COR3), The University of Queensland, Brisbane, QLD 4006, Australia
- School of Dentistry, Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, QLD 4006, Australia
| | - Sašo Ivanovski
- Center for Oral-facial Regeneration, Rehabilitation and Reconstruction (COR3), The University of Queensland, Brisbane, QLD 4006, Australia
- School of Dentistry, Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, QLD 4006, Australia
| | - Pingping Han
- Center for Oral-facial Regeneration, Rehabilitation and Reconstruction (COR3), The University of Queensland, Brisbane, QLD 4006, Australia
- School of Dentistry, Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, QLD 4006, Australia
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14
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Wojciech Tynior, Joanna Katarzyna Strzelczyk. A Brief Landscape of Epigenetic Mechanisms in Dental Pathologies. CYTOL GENET+ 2022. [DOI: 10.3103/s0095452722050115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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15
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Larsson L, Kavanagh NM, Nguyen TVN, Castilho RM, Berglundh T, Giannobile WV. Influence of epigenetics on periodontitis and peri-implantitis pathogenesis. Periodontol 2000 2022; 90:125-137. [PMID: 35913702 DOI: 10.1111/prd.12453] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Periodontitis is a disease characterized by tooth-associated microbial biofilms that drive chronic inflammation and destruction of periodontal-supporting tissues. In some individuals, disease progression can lead to tooth loss. A similar condition can occur around dental implants in the form of peri-implantitis. The immune response to bacterial challenges is not only influenced by genetic factors, but also by environmental factors. Epigenetics involves the study of gene function independent of changes to the DNA sequence and its associated proteins, and represents a critical link between genetic and environmental factors. Epigenetic modifications have been shown to contribute to the progression of several diseases, including chronic inflammatory diseases like periodontitis and peri-implantitis. This review aims to present the latest findings on epigenetic influences on periodontitis and to discuss potential mechanisms that may influence peri-implantitis, given the paucity of information currently available.
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Affiliation(s)
- Lena Larsson
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA.,Department of Periodontology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Nolan M Kavanagh
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Trang V N Nguyen
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
| | - Rogerio M Castilho
- Department of Periodontics and Oral Medicine and Laboratory of Epithelial Biology, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
| | - Tord Berglundh
- Department of Periodontology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - William V Giannobile
- Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA
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16
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Gabusi A, Gissi DB, Grillini S, Stefanini M, Tarsitano A, Marchetti C, Foschini MP, Montebugnoli L, Morandi L. Shared epigenetic alterations between oral cancer and periodontitis: a preliminary study. Oral Dis 2022. [PMID: 35567390 DOI: 10.1111/odi.14251] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 04/13/2022] [Accepted: 05/11/2022] [Indexed: 11/28/2022]
Abstract
INTRODUCTION We recently developed a non-invasive sampling procedure for oral squamous cell carcinoma (OSCC) detection based on DNA methylation analysis of a panel of 13 genes. Oral cancer, as well as acute and chronic inflammatory diseases, may influence the methylation level of several genes in the oral cavity. In the present study, we evaluated the presence of periodontal disease(PD) and the methylation status using our 13-gene panel. METHODS Oral brushing specimens were collected from three different patient groups: 23 gingival OSCC patients, 15 patients affected by PD, and 15 healthy volunteers lacking evidence of PD. DNA methylation analysis was performed and each sample was determined to be positive or negative based on a predefined cut-off value. RESULTS Positive results were found for 23/23 OSCC patients, 3/15 PD patients and 0/15 samples from healthy volunteers. The GP1BB and MIR193 genes in the PD group exhibited mean methylation levels similar to OSCC patients. ZAP70 showed different methylation levels among three groups. CONCLUSION Preliminary data identified shared epigenetic alterations between PD and OSCC patients in two inflammatory genes(GP1BB and MIR193). This study may help identify potential links between the two diseases and serve as a starting point for future research focused on pathogenesis.
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Affiliation(s)
- Andrea Gabusi
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Davide B Gissi
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Sara Grillini
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Martina Stefanini
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Achille Tarsitano
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy.,Oral and Maxillo-facial Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna
| | - Claudio Marchetti
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy.,Oral and Maxillo-facial Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna
| | - Maria Pia Foschini
- Section of Anatomic Pathology at Bellaria Hospital, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
| | - Lucio Montebugnoli
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Luca Morandi
- Functional MR Unit, IRCCS Istituto delle Scienze Neurologiche di Bologna, Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy.,IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
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17
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Bezerra B, Monajemzadeh S, Silva D, Pirih FQ. Modulating the Immune Response in Periodontitis. FRONTIERS IN DENTAL MEDICINE 2022. [DOI: 10.3389/fdmed.2022.879131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Periodontitis is a chronic inflammatory condition initiated by the accumulation of bacterial biofilm. It is highly prevalent and when left untreated can lead to tooth loss. The presence of bacterial biofilm is essential for the initiation of the inflammatory response but is not the sole initiator. Currently it is unknown which mechanisms drive the dysbiosis of the bacterial biofilm leading to the dysregulation of the inflammatory response. Other players in this equation include environmental, systemic, and genetic factors which can play a role in exacerbating the inflammatory response. Treatment of periodontal disease consists of removal of the bacterial biofilm with the goal of resolving the inflammatory response; however, this does not occur in every case. Understanding the way the inflammatory response does not return to a state of homeostasis has led investigators to consider both systemic and local pharmacological interventions. Nonetheless, a better understanding of the impact that genetics and environmental factors may have on the inflammatory response could be key to helping identify how inflammation can be modulated therefore stopping the destruction of the periodontium. In this article, we will explore the current evidence associating the microbial dysbiosis and the dysregulation of the immune response, potential mechanisms or pathways that may be targeted for the modulation of the inflammatory response, and discuss the advantages and drawbacks associated with local and systemic inflammatory modulation in the management of periodontal disease. This information will be valuable for those interested in understanding potential adjunct methods for managing periodontal diseases, but not limited to, dental professionals, clinical researchers and the public at large.
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18
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Bordagaray MJ, Fernández A, Astorga J, Garrido M, Hernández P, Chaparro A, Lira MJ, Gebicke-Haerter P, Hernández M. CpG Single-Site Methylation Regulates TLR2 Expression in Proinflammatory PBMCs From Apical Periodontitis Individuals. Front Immunol 2022; 13:861665. [PMID: 35300329 PMCID: PMC8921253 DOI: 10.3389/fimmu.2022.861665] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 02/09/2022] [Indexed: 12/19/2022] Open
Abstract
Introduction Apical periodontitis (AP) is a common oral disease caused by the inflammatory destruction of the periapical tissues due to the infection of the root canal system of the tooth. It also contributes to systemic bacterial translocation, where peripheric mononuclear blood cells (PBMCs) can act as carriers. Toll-like receptor (TLR) 2 mediates the response to infection and activates inflammatory responses. DNA methylation can be induced by bacteria and contributes to the modulation of this response. Despite the evidence that supports the participation of PBMCs in immune-inflammatory disorders, the inflammatory profile and epigenetic regulatory mechanisms of PBMCs in AP individuals are unknown. Aim To determine TLR2 gene methylation and inflammatory profiles of PBMCs in AP. Methods Cross-sectional exploratory study. Otherwise, healthy individuals with AP (n=27) and controls (n=30) were included. PMBCs were isolated by a Ficoll gradient, cultured for 24 hours, and both RNA and DNA were extracted. DNA was bisulfite-treated, and specific sites at the promoter region of the TLR2 gene were amplified by qPCR using validated primers. To verify its amplification, agarose gels were performed. Then, the PCR product was sequenced. mRNA expression of TLR2 was determined by qPCR. The soluble levels of 105 inflammatory mediators were first explored with Proteome Profiler Human Cytokine Array Kit. Consequently, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, IL-6Rα, IL-1β, and IL-12p70 levels were measured by Multiplex assay. Results PBMCs from individuals with AP demonstrated a proinflammatory profile showing higher soluble levels of TNF-α, IL-6, and IL-1β compared to controls (p<0.05). Higher TLR2 expression and higher global methylation pattern of the promoter region of the gene were found in AP compared to controls (p<0.05). The CpGs single-sites at positions -166 and -146 were completely methylated, while the site -102 was totally unmethylated, independently of the presence of AP. DNA methylation of CpG single-sites in positions -77 and +24 was positively associated with TLR2 expression. Conclusions PBMCs from AP subjects show a hyperinflammatory phenotype and TLR2 upregulation in association with single CpG-sites’ methylation from the TLR2 gene promoter, thereby contributing to a sustained systemic inflammatory load in individuals with periapical endodontic diseases.
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Affiliation(s)
- María José Bordagaray
- Laboratory of Periodontal Biology, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.,Department of Conservative Dentistry, Faculty of Dentistry, Universidad de Chile, Santiago, Chile
| | - Alejandra Fernández
- Laboratory of Periodontal Biology, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.,Faculty of Dentistry, Universidad Andres Bello, Santiago, Chile
| | - Jessica Astorga
- Laboratory of Periodontal Biology, Faculty of Dentistry, Universidad de Chile, Santiago, Chile
| | - Mauricio Garrido
- Laboratory of Periodontal Biology, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.,Department of Conservative Dentistry, Faculty of Dentistry, Universidad de Chile, Santiago, Chile
| | - Patricia Hernández
- Laboratory of Periodontal Biology, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.,Department of Conservative Dentistry, Faculty of Dentistry, Universidad de Chile, Santiago, Chile
| | - Alejandra Chaparro
- Department of Periodontology, Faculty of Dentistry, Centro de Investigación e Innovación Biomédica (CIIB), Universidad de Los Andes, Santiago, Chile
| | - María Jesús Lira
- Department of Orthopedic Surgery, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Peter Gebicke-Haerter
- Institute of Psychopharmacology, Central Institute of Mental Health, Faculty of Medicine, University of Heidelberg, Mannheim, Germany
| | - Marcela Hernández
- Laboratory of Periodontal Biology, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.,Department of Pathology and Oral Medicine, Faculty of Dentistry, Universidad de Chile, Santiago, Chile
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19
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Yang T, Cheng B, Noble JM, Reitz C, Papapanou PN. Replication of gene polymorphisms associated with periodontitis-related traits in an elderly cohort: the Washington Heights/Inwood Community Aging Project Ancillary Study of Oral Health. J Clin Periodontol 2022; 49:414-427. [PMID: 35179257 PMCID: PMC9012699 DOI: 10.1111/jcpe.13605] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 02/10/2022] [Indexed: 11/28/2022]
Abstract
AIM We sought to replicate findings from published genome-wide association studies (GWAS), linking specific candidate gene loci with periodontitis-related clinical/microbial traits. MATERIALS AND METHODS In the published GWAS, a total of 2196 single nucleotide polymorphisms associated with periodontitis-related traits at a p ≤ 5 × 10-6 and mapped to 136 gene loci. The replication cohort included 1124 individuals, 65-98 years old (67% female, 45% Hispanic, 30% Black, 23% White) with available genome-wide genotypes and full-mouth periodontal status. Microbial profiles using checkerboard DNA-DNA hybridization and 16SrRNA sequencing were available from 912 and 739 participants, respectively. RESULTS Using gene-specific p-values after linkage disequilibrium pruning, the following gene/phenotype associations replicated successfully: CLEC19A with edentulism and %teeth with pocket depth (PD) ≥4 mm; IL37, HPVC1, TRPS1, ABHD12B, LDLRAD4 (C180rF1), TGM3, and GRK5 with %teeth with PD ≥4 mm; DAB2IP with presence of PD ≥6 mm; KIAA1715(LNPK), ROBO2, RAB28, LINC01017, NELL1, LDLRAD4(C18orF1), and CRYBB2P1 with %teeth with clinical attachment level (CAL) ≥3 mm; RUNX2 and LAMA2 with %teeth with CAL ≥5 mm; and KIAA1715(LNPK) with high colonization by Aggregatibacter actinomycetemcomitans. In addition, CLEC19A, IQSEC1, and EMR1 associated with microbial abundance based on checkerboard data, LBP and NCR2 with abundance based on sequencing data, and NCR2 with microbial diversity based on sequencing data. CONCLUSIONS Several gene loci identified in published GWAS as associated with periodontitis-related phenotypes replicated successfully in an elderly cohort.
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Affiliation(s)
- Teresa Yang
- Division of Periodontics, Section of Oral, Diagnostic and Rehabilitation Sciences, College of Dental Medicine, Columbia University, New York, New York, USA
| | - Bin Cheng
- Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York, USA
| | - James M Noble
- Taub Institute for Research on Alzheimer's Disease and the Aging Brain, GH Sergievsky Center and Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA
| | - Christiane Reitz
- Taub Institute for Research on Alzheimer's Disease and the Aging Brain, GH Sergievsky Center and Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA
| | - Panos N Papapanou
- Division of Periodontics, Section of Oral, Diagnostic and Rehabilitation Sciences, College of Dental Medicine, Columbia University, New York, New York, USA
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20
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Rapone B, Ferrara E, Santacroce L, Topi S, Gnoni A, Dipalma G, Mancini A, Di Domenico M, Tartaglia GM, Scarano A, Inchingolo F. The Gaseous Ozone Therapy as a Promising Antiseptic Adjuvant of Periodontal Treatment: A Randomized Controlled Clinical Trial. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19020985. [PMID: 35055807 PMCID: PMC8775443 DOI: 10.3390/ijerph19020985] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Revised: 01/07/2022] [Accepted: 01/12/2022] [Indexed: 01/27/2023]
Abstract
Background: the establishment of periodontitis is regulated by the primary etiological factor and several individual conditions including the immune response mechanism of the host and individual genetic factors. It results when the oral homeostasis is interrupted, and biological reactions favor the development and progression of periodontal tissues damage. Different strategies have been explored for reinforcing the therapeutic effect of non-surgical periodontal treatment of periodontal tissue damage. Gaseous ozone therapy has been recognized as a promising antiseptic adjuvant, because of its immunostimulating, antimicrobial, antihypoxic, and biosynthetic effects. Then, we hypothesized that the adjunct of gaseous ozone therapy to standard periodontal treatment may be leveraged to promote the tissue healing response. Methods: to test this hypothesis, we conducted a prospective randomized study comparing non-surgical periodontal treatment plus gaseous ozone therapy to standard therapy. A total of 90 healthy individuals with moderate or severe generalized periodontitis were involved in the study. The trial was conducted from September 2019 to October 2020. Forty-five patients were randomized to receive scaling and root-planning (SRP) used as conventional non-surgical periodontal therapy plus gaseous ozone therapy (GROUP A); forty-five were allocated to standard treatment (GROUP B). The endpoint was defined as the periodontal response rate after the application of the ozone therapy at 3 months and 6 months, defined as no longer meeting the criteria for active periodontitis. Statistical analysis was performed employing SPSS v.18 Chicago: SPSS Inc. Results: periodontal parameters differed significantly between patients treated with the two distinct procedures at 3 months (p ≤ 0.005); a statistically significant difference between groups was observed from baseline in the CAL (p ≤ 0.0001), PPD (p ≤ 0.0001) and BOP (p ≤ 0.0001) scores. Conclusions: The present study suggests that SRP combined with ozone therapy in the treatment of periodontitis revealed an improved outcome than SRP alone.
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Affiliation(s)
- Biagio Rapone
- Interdisciplinary Department of Medicine, “Aldo Moro” University of Bari, 70121 Bari, Italy; (G.D.); (A.M.); (F.I.)
- Correspondence: ; Tel.: +39-347-7619-817
| | - Elisabetta Ferrara
- Complex Operative Unit of Odontostomatology, Hospital S.S. Annunziata, 66100 Chieti, Italy; (E.F.); (L.S.)
| | - Luigi Santacroce
- Complex Operative Unit of Odontostomatology, Hospital S.S. Annunziata, 66100 Chieti, Italy; (E.F.); (L.S.)
| | - Skender Topi
- Department of Clinical Disciplines, School of Technical Medical Sciences, University A. Xhuvani, 3001 Elbasan, Albania;
| | - Antonio Gnoni
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, “Aldo Moro” University of Bari, 70121 Bari, Italy;
| | - Gianna Dipalma
- Interdisciplinary Department of Medicine, “Aldo Moro” University of Bari, 70121 Bari, Italy; (G.D.); (A.M.); (F.I.)
| | - Antonio Mancini
- Interdisciplinary Department of Medicine, “Aldo Moro” University of Bari, 70121 Bari, Italy; (G.D.); (A.M.); (F.I.)
| | - Marina Di Domenico
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy;
| | - Gianluca Martino Tartaglia
- UOC Maxillo-Facial Surgery and Dentistry, Department of Biomedical, Surgical and Dental Sciences, School of Dentistry, Fondazione IRCCS Ca Granda, Ospedale Maggiore Policlinico, University of Milan, 20100 Milan, Italy;
| | - Antonio Scarano
- Department of Oral Science, Nano and Biotechnology and CeSi-Met University of Chieti-Pescara, 66100 Chieti, Italy;
| | - Francesco Inchingolo
- Interdisciplinary Department of Medicine, “Aldo Moro” University of Bari, 70121 Bari, Italy; (G.D.); (A.M.); (F.I.)
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Salivary Pro-Inflammatory Markers and Smoking Status Influences the Treatment Effectiveness of Periodontal Disease Patients with Hypertension. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18147364. [PMID: 34299815 PMCID: PMC8305443 DOI: 10.3390/ijerph18147364] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 06/24/2021] [Accepted: 07/06/2021] [Indexed: 11/17/2022]
Abstract
BACKGROUND Hypertension and periodontal diseases share several risk factors. Inflammation biomarkers in saliva are related to hypertension and periodontal disease. The aim of this study was to explore the role of the salivary inflammatory biomarkers in the treatment effectiveness of patients with hypertension and periodontal disease. METHODS This observational study enrolled 160 subjects diagnosed with periodontitis, 40 of which had a history of hypertension. All subjects had completed scaling and root planning therapeutic procedures within four weeks. The clinical periodontal parameters (i.e., bleeding on probing, plaque control record (PCR), and probing depth (PD)) were evaluated before and after the treatment. Pro-inflammatory markers were determined using a commercial kit. RESULTS The recovery rate (PD 4-9 mm) in non-hypertensive subjects was significantly higher than in hypertensive subjects (60.47% vs. 52.60%, respectively; p = 0.04). All clinical parameters, excluding PCR, positively correlated with salivary IL-1β at baseline and after completing treatment. Our results showed that increased salivary IL-1β levels were positively associated with decreased PCR (β = -27.65 and p = 0.05) and PD recovery rate (β = -17.05 and p = 0.02) in hypertensive subjects. CONCLUSIONS The present study sheds important light on the clinical use of salivary pro-inflammatory cytokines as valuable biomarkers for predicting the treatment effectiveness of patients suffering from hypertension and periodontitis.
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22
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Gasparoni LM, Alves FA, Holzhausen M, Pannuti CM, Serpa MS. Periodontitis as a risk factor for head and neck cancer. Med Oral Patol Oral Cir Bucal 2021; 26:e430-e436. [PMID: 33340075 PMCID: PMC8254889 DOI: 10.4317/medoral.24270] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 12/08/2020] [Indexed: 01/20/2023] Open
Abstract
Background Periodontitis may be associated with the development of head and neck cancer (HNC). A literature review was conducted to understand the possible association between them.
Material and Methods Articles published in the PubMed database from January 1999 and May 2020 were retrieved. Limitations of the studies and biological mechanisms were discussed.
Results A total of 4,232 articles were found. Of these, 13 were analyzed according to inclusion criteria. Most papers found some association between periodontitis and HNC, although differences in periodontal evaluation, sample size, study design and tumor sites were observed. Porphyromonas gingivalis appears to increase the chance of both diseases, and it may be one of their main potential risk factors. Genetic predisposition is increased by exposure to environmental factors which can directly induce epigenetic changes that contribute to these diseases.
Conclusions Understanding the mechanisms related to periodontitis and HNC has increased, however, well-designed clinical studies are needed for better conclusions. Furthermore, the advent of multiple "omic" technologies will help comprehend their possible association. Key words:Periodontitis, head and neck cancer, oral cancer, risk factors, biological factors.
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Affiliation(s)
- L-M Gasparoni
- Department of Stomatology A.C.Camargo Cancer Center São Paulo, Brazil
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Cho YD, Kim WJ, Ryoo HM, Kim HG, Kim KH, Ku Y, Seol YJ. Current advances of epigenetics in periodontology from ENCODE project: a review and future perspectives. Clin Epigenetics 2021; 13:92. [PMID: 33902683 PMCID: PMC8077755 DOI: 10.1186/s13148-021-01074-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Accepted: 04/12/2021] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND The Encyclopedia of DNA Elements (ENCODE) project has advanced our knowledge of the functional elements in the genome and epigenome. The aim of this article was to provide the comprehension about current research trends from ENCODE project and establish the link between epigenetics and periodontal diseases based on epigenome studies and seek the future direction. MAIN BODY Global epigenome research projects have emphasized the importance of epigenetic research for understanding human health and disease, and current international consortia show an improved interest in the importance of oral health with systemic health. The epigenetic studies in dental field have been mainly conducted in periodontology and have focused on DNA methylation analysis. Advances in sequencing technology have broadened the target for epigenetic studies from specific genes to genome-wide analyses. CONCLUSIONS In line with global research trends, further extended and advanced epigenetic studies would provide crucial information for the realization of comprehensive dental medicine and expand the scope of ongoing large-scale research projects.
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Affiliation(s)
- Young-Dan Cho
- Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital, Yeongeon-dong, Jongno-gu, Seoul, 03080, Korea
| | - Woo-Jin Kim
- Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea
| | - Hyun-Mo Ryoo
- Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea
| | - Hong-Gee Kim
- Biomedical Knowledge Engineering Laboratory, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea
| | - Kyoung-Hwa Kim
- Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital, Yeongeon-dong, Jongno-gu, Seoul, 03080, Korea
| | - Young Ku
- Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital, Yeongeon-dong, Jongno-gu, Seoul, 03080, Korea
| | - Yang-Jo Seol
- Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital, Yeongeon-dong, Jongno-gu, Seoul, 03080, Korea.
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Feng Z, Meng R, Li Q, Li D, Xu Q. 5-aza-2'-deoxycytidine may regulate the inflammatory response of human odontoblast-like cells through the NF-κB pathway. Int Endod J 2021; 54:1105-1117. [PMID: 33539038 DOI: 10.1111/iej.13488] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 01/29/2021] [Accepted: 02/02/2021] [Indexed: 11/28/2022]
Abstract
AIM To explore the role of DNA methylation in the innate immunity of the dental pulp, this study investigated the effect of 5-aza-2'-deoxycytidine (AZA) on lipoteichoic acid (LTA)-induced cytokine production and related intracellular signalling pathways in human odontoblast-like cells (hOBs). METHODOLOGY hOBs were cultured and differentiated from human dental pulp tissue, and the odontoblastic phenotype of the cells was detected using immunofluorescence, qRT-PCR and Western blotting. hOBs were pretreated with AZA and then stimulated with 10 μg mL-1 LTA. The levels of 42 cytokines related to immunity and inflammation were examined using a cytokine antibody array and verified using qRT-PCR and ELISA. The effect of AZA on the LTA-induced NF-κB and MAPK signalling pathways was explored using Western blotting. The cells were treated with the specific NF-κB inhibitor PDTC and MAPK inhibitors (the ERK inhibitor U0126, the p38 inhibitor SB203580, and the JNK inhibitor SP600125) to further confirm the role of the signalling pathways in LTA-treated hOBs. DNA immunoprecipitation-PCR was used to examine the dynamic methylation status of the gene promoters of myeloid differentiation primary response 88 (MyD88) and tumour necrosis factor receptor-associated factor 6 (TRAF6) in the LTA-induced hOBs. Statistical analyses of the differences between two groups were performed using Student's t-test. One-way analysis of variance (anova) or repeated-measures anova with a post hoc Dunnett's test was used to assess the differences between multiple sets of data. P < 0.05 was considered to be statistically significant. RESULTS The odontoblastic markers were significantly higher in hOBs than those in human dental pulp cells (hDPCs) (P < 0.05). According to the cytokine antibody array results, hOBs pretreated with AZA had significantly increased production of several inflammatory cytokines (P < 0.05), in which the expression levels of IL-6 and IL-8 were the most dramatically increased upon LTA stimulation (P < 0.01). Furthermore, AZA resulted in the significant upregulation of p-IKKα/β, p-IκBα, p-p65, p-p38 and p-ERK in LTA-stimulated hOBs (P < 0.01). Treatment with the NF-κB pathway inhibitor suppressed both IL-6 and IL-8 expression (P < 0.05), whereas inhibitors of the MAPK pathway (SB203580 and SP600125) did not. In LTA-treated hOBs, AZA significantly increased the expression levels of TRAF6 and MyD88 (P < 0.05). AZA induced MyD88 promoter hypomethylation but did not affect TRAF6 methylation. CONCLUSION AZA regulated the LTA-induced inflammatory response through the NF-κB signal pathway in hOBs. This study highlights the important role of DNA methylation in the immunity defence of odontoblasts during the dental pulp immunity response to caries.
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Affiliation(s)
- Z Feng
- Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - R Meng
- Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.,Department of Stomatology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Q Li
- Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - D Li
- Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Q Xu
- Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
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Decitabine Inhibits Bone Resorption in Periodontitis by Upregulating Anti-Inflammatory Cytokines and Suppressing Osteoclastogenesis. Biomedicines 2021; 9:biomedicines9020199. [PMID: 33671221 PMCID: PMC7922804 DOI: 10.3390/biomedicines9020199] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 02/12/2021] [Accepted: 02/13/2021] [Indexed: 12/14/2022] Open
Abstract
DNA methylation controls several inflammatory genes affecting bone homeostasis. Hitherto, inhibition of DNA methylation in vivo in the context of periodontitis and osteoclastogenesis has not been attempted. Ligature-induced periodontitis in C57BL/6J mice was induced by placing ligature for five days with Decitabine (5-aza-2′-deoxycytidine) (1 mg/kg/day) or vehicle treatment. We evaluated bone resorption, osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) and mRNA expression of anti-inflammatory molecules using cluster differentiation 14 positive (CD14+) monocytes from human peripheral blood. Our data showed that decitabine inhibited bone loss and osteoclast differentiation experimental periodontitis, and suppressed osteoclast CD14+ human monocytes; and conversely, that it increased bone mineralization in osteoblastic cell line MC3T3-E1 in a concentration-dependent manner. In addition to increasing IL10 (interleukin-10), TGFB (transforming growth factor beta-1) in CD14+ monocytes, decitabine upregulated KLF2 (Krüppel-like factor-2) expression. Overexpression of KLF2 protein enhanced the transcription of IL10 and TGFB. On the contrary, site-directed mutagenesis of KLF2 binding site in IL10 and TFGB abrogated luciferase activity in HEK293T cells. Decitabine reduces bone loss in a mouse model of periodontitis by inhibiting osteoclastogenesis through the upregulation of anti-inflammatory cytokines via KLF2 dependent mechanisms. DNA methyltransferase inhibitors merit further investigation as a possible novel therapy for periodontitis.
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26
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de Andrade DR, Silva PA, Colombo APV, Silva-Boghossian CM. Subgingival microbiota in overweight and obese young adults with no destructive periodontal disease. J Periodontol 2021; 92:1410-1419. [PMID: 33386623 DOI: 10.1002/jper.20-0187] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 10/13/2020] [Accepted: 12/27/2020] [Indexed: 12/27/2022]
Abstract
BACKGROUND This study analyzed the levels of a specific group of periodontal health/disease-related oral bacteria in the subgingival biofilm of young adults with overweight (OW) and obesity (OB), and no destructive periodontal disease. METHODS Full-mouth periodontal assessment and subgingival biofilm sampling were performed in individuals with normal weight (NW) (BMI [body mass index] ≥18.5 to ≤24.9 kg/m2 ; n = 29), OW (BMI ≥25 to ≤29.9 kg/m2 ; n = 26), or OB (BMI ≥30 kg/m2 ; n = 22). BMI, waist (WC) and hip (HC) circumferences, and waist-hip ratio (WHR) were established for every individual. Biofilm samples were analyzed by checkerboard. Spearman coefficient, linear, and logistic regression analyses were obtained. RESULTS Gingivitis was detected in 45% NW, 65% OW, and 73% OB individuals. NW patients presented significantly less calculus and supragingival biofilm than OB. OW, and OB individuals had significantly higher levels of Porphyromonas gingivalis and Tannerella forsythia than NW patients (P <0.05). Treponema denticola correlated with BMI (rho = 0.31), WC (rho = 0.28), and HC (rho = 0.29), P≤0.01. Linear regression analysis showed significant (P <0.05) positive associations between BMI, WC, HC, and WHR indicators and Prevotella spp., Lactobacillus spp., V. parvula, and A. actinomycetemcomitans (Aa); negative associations were found between Capnocytophaga spp., WC, and HC (β = -0.29 and β = -0.37, respectively; P <0.01). However, the interaction of Prevotella spp. and T. forsythia decreased the likelihood of an individual to be diagnosed as OW/OB (OR 0.183 [95% CI, 0.062-0.540]). CONCLUSIONS Few periodontal pathogens differed in levels between NW and OW/OB individuals without destructive periodontal disease. Moreover, Aa, T. denticola, and Prevotella spp. were associated with clinical parameters of obesity.
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Affiliation(s)
- Danielle Rodrigues de Andrade
- Postgraduate Program in Translational Biomedicine, University of Grande Rio, Duque de Caxias, Rio de Janeiro, Brazil
| | - Paulo André Silva
- Postgraduate Program in Translational Biomedicine, University of Grande Rio, Duque de Caxias, Rio de Janeiro, Brazil
| | - Ana Paula V Colombo
- Department of Medical Microbiology, Institute of Microbiology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Carina Maciel Silva-Boghossian
- Postgraduate Program in Translational Biomedicine, University of Grande Rio, Duque de Caxias, Rio de Janeiro, Brazil.,Postgraduate Program in Dentistry, University of Grande Rio, Duque de Caxias, Rio de Janeiro, Brazil
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27
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Zhang RC, Du WQ, Zhang JY, Yu SX, Lu FZ, Ding HM, Cheng YB, Ren C, Geng DQ. Mesenchymal stem cell treatment for peripheral nerve injury: a narrative review. Neural Regen Res 2021; 16:2170-2176. [PMID: 33818489 PMCID: PMC8354135 DOI: 10.4103/1673-5374.310941] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Peripheral nerve injuries occur as the result of sudden trauma and lead to reduced quality of life. The peripheral nervous system has an inherent capability to regenerate axons. However, peripheral nerve regeneration following injury is generally slow and incomplete that results in poor functional outcomes such as muscle atrophy. Although conventional surgical procedures for peripheral nerve injuries present many benefits, there are still several limitations including scarring, difficult accessibility to donor nerve, neuroma formation and a need to sacrifice the autologous nerve. For many years, other therapeutic approaches for peripheral nerve injuries have been explored, the most notable being the replacement of Schwann cells, the glial cells responsible for clearing out debris from the site of injury. Introducing cultured Schwann cells to the injured sites showed great benefits in promoting axonal regeneration and functional recovery. However, there are limited sources of Schwann cells for extraction and difficulties in culturing Schwann cells in vitro. Therefore, novel therapeutic avenues that offer maximum benefits for the treatment of peripheral nerve injuries should be investigated. This review focused on strategies using mesenchymal stem cells to promote peripheral nerve regeneration including exosomes of mesenchymal stem cells, nerve engineering using the nerve guidance conduits containing mesenchymal stem cells, and genetically engineered mesenchymal stem cells. We present the current progress of mesenchymal stem cell treatment of peripheral nerve injuries.
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Affiliation(s)
- Rui-Cheng Zhang
- Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
| | - Wen-Qi Du
- Department of Human Anatomy, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
| | - Jing-Yuan Zhang
- Department of Neurosurgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong Province, China
| | - Shao-Xia Yu
- Department of Neurology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong Province, China
| | - Fang-Zhi Lu
- Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
| | - Hong-Mei Ding
- Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
| | - Yan-Bo Cheng
- Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
| | - Chao Ren
- Department of Neurology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong Province, China
| | - De-Qin Geng
- Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
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28
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Stanisic D, Jovanovic M, George AK, Homme RP, Tyagi N, Singh M, Tyagi SC. Gut microbiota and the periodontal disease: role of hyperhomocysteinemia. Can J Physiol Pharmacol 2021; 99:9-17. [PMID: 32706987 DOI: 10.1139/cjpp-2020-0215] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Periodontal disease is one of the most common conditions resulting from poor oral hygiene and is characterized by a destructive process in the periodontium that essentially includes gingiva, alveolar mucosa, cementum, periodontal ligament, and alveolar bone. Notably, the destructive event in the alveolar bone has been linked to homocysteine (Hcy) metabolism; however, it has not been fully investigated. Therefore; the implication of Hcy towards initiation, progression, and maintenance of the periodontal disease remains incompletely understood. Higher levels of Hcy (also known as hyperhomocysteinemia (HHcy)) exerts deleterious effects on gum health and teeth in distinct ways. Firstly, increased production of proinflammatory cytokines such as TNF-α, IL-1β, IL-6, and IL-8 leads to an inflammatory cascade of events that affect methionine (Met) and Hcy metabolism (i.e., 1-carbon metabolism) leading to HHcy. Secondly, metabolic dysregulation during chronic medical conditions increases systemic inflammation leading to a decrease in vitamins, more specifically B6, B12, and folic acid, that play important roles as cofactors in Hcy metabolism. Also, given the folate level in the HHcy state that is important during dysbiosis, these two conditions appear to be intimately related, and in this context, HHcy-induced dysbiosis may be one of the potential causes of periodontal disease. This paper sums up the link between periodontitis and HHcy, with a special emphasis on the "oral-gut microbiome axis" and the potential probiotic intervention towards warding off some of the serious periodontal disease conditions.
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Affiliation(s)
- Dragana Stanisic
- Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
| | - Milica Jovanovic
- Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
| | - Akash K George
- Department of Physiology, University of Louisville School of Medicine, Louisville, KY 40202, USA
| | - Rubens P Homme
- Department of Physiology, University of Louisville School of Medicine, Louisville, KY 40202, USA
| | - Neetu Tyagi
- Department of Physiology, University of Louisville School of Medicine, Louisville, KY 40202, USA
| | - Mahavir Singh
- Department of Physiology, University of Louisville School of Medicine, Louisville, KY 40202, USA
| | - Suresh C Tyagi
- Department of Physiology, University of Louisville School of Medicine, Louisville, KY 40202, USA
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29
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Puletic M, Popovic B, Jankovic S, Brajovic G. Detection rates of periodontal bacteria and herpesviruses in different forms of periodontal disease. Microbiol Immunol 2020; 64:815-824. [PMID: 33107981 DOI: 10.1111/1348-0421.12857] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 10/07/2020] [Accepted: 10/20/2020] [Indexed: 01/02/2023]
Abstract
The aim was to investigate the detection rates of periodontal bacteria (Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans) and herpesviruses (herpes simplex virus-1 [HSV-1], cytomegalovirus [CMV], and Epstein-Barr virus [EBV]) in different forms and severity of periodontal disease, and to compare them with those in periodontally healthy subjects. One hundred and twenty-nine patients participated in the study: 39 diagnosed with periodontal abscess (PA), 33 with necrotizing ulcerative periodontitis (NUP), 27 with chronic periodontitis (CP), and 30 participants with healthy periodontal tissue represented a healthy control group. All patients with periodontal disease (PA, NUP, and CP) were also divided into two groups according to the severity of their disease: moderate and severe periodontitis. The subgingival samples were collected from the periodontitis active sites and the detection of microorganisms was performed by end-point polymerase chain reaction analyses. The results revealed significantly higher detection rates of P. gingivalis, T. forsythia, and P. intermedia in all three groups of patients with periodontitis than in healthy participants. The highest detection rate of A. actinomycetemcomitans was noticed in CP, which was significantly higher than that in PA, NUP, and healthy control. The occurrence of EBV was significantly higher in NUP than in CP and healthy participants. CMV was detected significantly more frequently in PA and NUP than in CP and healthy participants. Comparisons among healthy participants and patients with moderate and severe periodontitis showed significantly higher detection rates of EBV and CMV in patients with severe forms of periodontitis than in healthy participants and those with moderate periodontitis.
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Affiliation(s)
- Miljan Puletic
- Clinic for Periodontology and Oral Medicine, School of Dental Medicine, University of Belgrade, Belgrade, Serbia
| | - Branka Popovic
- Department of Human Genetics, School of Dental Medicine, University of Belgrade, Belgrade, Serbia
| | - Sasa Jankovic
- Clinic for Periodontology and Oral Medicine, School of Dental Medicine, University of Belgrade, Belgrade, Serbia
| | - Gavrilo Brajovic
- Department of Physiology, School of Dental Medicine, University of Belgrade, Belgrade, Serbia
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Jurdziński KT, Potempa J, Grabiec AM. Epigenetic regulation of inflammation in periodontitis: cellular mechanisms and therapeutic potential. Clin Epigenetics 2020; 12:186. [PMID: 33256844 PMCID: PMC7706209 DOI: 10.1186/s13148-020-00982-7] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 11/17/2020] [Indexed: 02/06/2023] Open
Abstract
Epigenetic mechanisms, namely DNA and histone modifications, are critical regulators of immunity and inflammation which have emerged as potential targets for immunomodulating therapies. The prevalence and significant morbidity of periodontitis, in combination with accumulating evidence that genetic, environmental and lifestyle factors cannot fully explain the susceptibility of individuals to disease development, have driven interest in epigenetic regulation as an important factor in periodontitis pathogenesis. Aberrant promoter methylation profiles of genes involved in inflammatory activation, including TLR2, PTGS2, IFNG, IL6, IL8, and TNF, have been observed in the gingival tissue, peripheral blood or buccal mucosa from patients with periodontitis, correlating with changes in expression and disease severity. The expression of enzymes that regulate histone acetylation, in particular histone deacetylases (HDACs), is also dysregulated in periodontitis-affected gingival tissue. Infection of gingival epithelial cells, gingival fibroblasts and periodontal ligament cells with the oral pathogens Porphyromonas gingivalis or Treponema denticola induces alterations in expression and activity of chromatin-modifying enzymes, as well as site-specific and global changes in DNA methylation profiles and in histone acetylation and methylation marks. These epigenetic changes are associated with excessive production of inflammatory cytokines, chemokines, and matrix-degrading enzymes that can be suppressed by small molecule inhibitors of HDACs (HDACi) or DNA methyltransferases. HDACi and inhibitors of bromodomain-containing BET proteins ameliorate inflammation, osteoclastogenesis, and alveolar bone resorption in animal models of periodontitis, suggesting their clinical potential as host modulation therapeutic agents. However, broader application of epigenomic methods will be required to create a comprehensive map of epigenetic changes in periodontitis. The integration of functional studies with global analyses of the epigenetic landscape will provide critical information on the therapeutic and diagnostic potential of epigenetics in periodontal disease.
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Affiliation(s)
- Krzysztof T Jurdziński
- Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland
| | - Jan Potempa
- Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.,Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, USA
| | - Aleksander M Grabiec
- Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
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31
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Liu Z, He Y, Xu C, Li J, Zeng S, Yang X, Han Q. The role of PHF8 and TLR4 in osteogenic differentiation of periodontal ligament cells in inflammatory environment. J Periodontol 2020; 92:1049-1059. [PMID: 33040333 DOI: 10.1002/jper.20-0285] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 09/25/2020] [Accepted: 09/29/2020] [Indexed: 12/28/2022]
Abstract
BACKGROUND Histone methylation is considered to play an important role in the occurrence and development of periodontitis. Plant homeodomain finger protein 8 (PHF8), a histone demethylase, has been shown to regulate inflammation and osteogenic differentiation of bone marrow stromal cells (BMSCs). This study aimed to detect the functions of PHF8 and TLR4 in osteogenic differentiation in an inflammatory environment induced by Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) METHODS: A periodontitis mouse model was established, and the mice were treated with TAK-242. Immunohistochemical staining was used to detect the expression of PHF8 in periodontal tissue. Periodontal ligament cells (PDLCs) were treated with mineralization induction medium supplemented with Pg-LPS and/or TAK-242, and a Cell Counting Kit-8 (CCK-8) assay was used to detect the proliferation of PDLCs. Real-time PCR and western blotting were used to detect the mRNA and protein expression levels, respectively, of PHF8, toll-like receptor 4 (TLR4) and the other osteogenic markers alkaline phosphatase (ALP), osteocalcin (OCN), Special AT-rich sequence-binding protein 2 (Satb2) and Runt-related transcription factor 2 (Runx2) RESULTS: Periodontitis reduced PHF8 expression in periodontal tissue, and TAK-242 partially reversed this downregulation. An in vitro experiment revealed that the mRNA and protein expression levels of PHF8 were significantly upregulated during the osteogenic differentiation of PDLCs. Alizarin red staining showed that the mineralized nodules of PDLCs in osteogenic induction group were more than those in control group. Real-time PCR and western blot results indicated that Pg-LPS inhibited PHF8 expression and upregulated TLR4 expression in PDLCs. TAK-242 inhibited TLR4 and partially reversed the inhibition of PHF8 expression and osteogenic differentiation induced by Pg-LPS in PDLCs CONCLUSION: PHF8 and TLR4 play important roles in periodontitis. Pg-LPS inhibits the expression of PHF8 via upregulation of TLR4 and might further inhibit the osteogenic differentiation of PDLCs. However, the specific mechanisms involved remain to be explored.
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Affiliation(s)
- Zhao Liu
- Department of endodontics, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Yiheng He
- School of Stomatology, Southern Medical University, Guangzhou, P.R. China
| | - Chenrong Xu
- Department of Periodontics, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Jianjia Li
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Shuguang Zeng
- Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Xi Yang
- Department of Periodontics, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Qianqian Han
- Department of Periodontics, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
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32
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Francis M, Gopinathan G, Foyle D, Fallah P, Gonzalez M, Luan X, Diekwisch T. Histone Methylation: Achilles Heel and Powerful Mediator of Periodontal Homeostasis. J Dent Res 2020; 99:1332-1340. [PMID: 32762486 PMCID: PMC7580172 DOI: 10.1177/0022034520932491] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
The packaging of DNA around nucleosomes exerts dynamic control over eukaryotic gene expression either by granting access to the transcriptional machinery in an open chromatin state or by silencing transcription via chromatin compaction. Histone methylation modification affects chromatin through the addition of methyl groups to lysine or arginine residues of histones H3 and H4 by means of histone methyl transferases or histone demethylases. Changes in histone methylation state modulate periodontal gene expression and have profound effects on periodontal development, health, and therapy. At the onset of periodontal development, progenitor cell populations such as dental follicle cells are characterized by an open H3K4me3 chromatin mark on RUNX2, MSX2, and DLX5 gene promoters. During further development, periodontal progenitor differentiation undergoes a global switch from the H3K4me3 active methyl mark to the H3K27me3 repressive mark. When compared with dental pulp cells, periodontal neural crest lineage differentiation is characterized by repressive H3K9me3 and H3K27me3 marks on typical dentinogenesis-related genes. Inflammatory conditions as they occur during periodontal disease result in unique histone methylation signatures in affected cell populations, including repressive H3K9me3 and H3K27me3 histone marks on extracellular matrix gene promoters and active H3K4me3 marks on interleukin, defensin, and chemokine gene promoters, facilitating a rapid inflammatory response to microbial pathogens. The inflammation-induced repression of chromatin on extracellular matrix gene promoters presents a therapeutic opportunity for the application of histone methylation inhibitors capable of inhibiting suppressive trimethylation marks. Furthermore, inhibition of chromatin coregulators through interference with key inflammatory mediators such as NF-kB by means of methyltransferase inhibitors provides another avenue to halt the exacerbation of the inflammatory response in periodontal tissues. In conclusion, histone methylation dynamics play an intricate role in the fine-tuning of chromatin states during periodontal development and harbor yet-to-be-realized potential for the treatment of periodontal disease.
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Affiliation(s)
- M. Francis
- Department of Oral Biology, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA
| | - G. Gopinathan
- Department of Periodontics and Center for Craniofacial Research and Diagnosis, Texas A&M University College of Dentistry, Dallas, TX, USA
| | - D. Foyle
- Department of Periodontics and Center for Craniofacial Research and Diagnosis, Texas A&M University College of Dentistry, Dallas, TX, USA
| | - P. Fallah
- Department of Periodontics and Center for Craniofacial Research and Diagnosis, Texas A&M University College of Dentistry, Dallas, TX, USA
| | - M. Gonzalez
- Department of Periodontics and Center for Craniofacial Research and Diagnosis, Texas A&M University College of Dentistry, Dallas, TX, USA
| | - X. Luan
- Department of Oral Biology, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA
- Department of Periodontics and Center for Craniofacial Research and Diagnosis, Texas A&M University College of Dentistry, Dallas, TX, USA
| | - T.G.H. Diekwisch
- Department of Oral Biology, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA
- Department of Periodontics and Center for Craniofacial Research and Diagnosis, Texas A&M University College of Dentistry, Dallas, TX, USA
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Mei HX, Chen YL, Shi PL, Yang SR, Xu X, He JZ. [Advances in oral bacteria influencing host epigenetic regulation]. HUA XI KOU QIANG YI XUE ZA ZHI = HUAXI KOUQIANG YIXUE ZAZHI = WEST CHINA JOURNAL OF STOMATOLOGY 2020; 38:583-588. [PMID: 33085246 DOI: 10.7518/hxkq.2020.05.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Epigenetics refers to a steady change in the level of gene expression caused by non-DNA sequence changes. Microbes can modulate host inflammation through epigenetic pathways to evade or expend immune responses. As an important part of human microbes, oral bacteria also have various epigenetic regulation mechanisms to affect host inflammatory responses. This article reviews the common pathways of epigenetic regulation in microbe infection and the regulation of host epigenetics by using oral microbes to provide a reference for the study of epigenetic-related mechanisms in oral diseases.
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Affiliation(s)
- Hong-Xiang Mei
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Yi-Lin Chen
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Pei-Lei Shi
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Si-Rui Yang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Xin Xu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Jin-Zhi He
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
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Khouly I, Braun RS, Ordway M, Aouizerat BE, Ghassib I, Larsson L, Asa’ad F. The Role of DNA Methylation and Histone Modification in Periodontal Disease: A Systematic Review. Int J Mol Sci 2020; 21:E6217. [PMID: 32867386 PMCID: PMC7503325 DOI: 10.3390/ijms21176217] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 08/08/2020] [Accepted: 08/11/2020] [Indexed: 02/07/2023] Open
Abstract
Despite a number of reports in the literature on the role of epigenetic mechanisms in periodontal disease, a thorough assessment of the published studies is warranted to better comprehend the evidence on the relationship between epigenetic changes and periodontal disease and its treatment. Therefore, the aim of this systematic review is to identify and synthesize the evidence for an association between DNA methylation/histone modification and periodontal disease and its treatment in human adults. A systematic search was independently conducted to identify articles meeting the inclusion criteria. DNA methylation and histone modifications associated with periodontal diseases, gene expression, epigenetic changes after periodontal therapy, and the association between epigenetics and clinical parameters were evaluated. Sixteen studies were identified. All included studies examined DNA modifications in relation to periodontitis, and none of the studies examined histone modifications. Substantial variation regarding the reporting of sample sizes and patient characteristics, statistical analyses, and methodology, was found. There was some evidence, albeit inconsistent, for an association between DNA methylation and periodontal disease. IL6, IL6R, IFNG, PTGS2, SOCS1, and TNF were identified as candidate genes that have been assessed for DNA methylation in periodontitis. While several included studies found associations between methylation levels and periodontal disease risk, there is insufficient evidence to support or refute an association between DNA methylation and periodontal disease/therapy in human adults. Further research must be conducted to identify reproducible epigenetic markers and determine the extent to which DNA methylation can be applied as a clinical biomarker.
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Affiliation(s)
- Ismael Khouly
- Department of Oral and Maxillofacial Surgery, College of Dentistry, New York University, New York, NY 10010, USA;
| | - Rosalie Salus Braun
- Department of Cariology and Comprehensive Care, College of Dentistry, New York University, New York, NY 10010, USA;
| | - Michelle Ordway
- Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;
| | - Bradley Eric Aouizerat
- Department of Oral and Maxillofacial Surgery, College of Dentistry, New York University, New York, NY 10010, USA;
- Bluestone Center for Clinical Research, New York University College of Dentistry, New York, NY 10010, USA
| | - Iya Ghassib
- Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, MI 48104, USA;
| | - Lena Larsson
- Department of Periodontology, Institute of Odontology, The Sahlgrenska Academy at University of Gothenburg, SE-405 30 Göteborg, Sweden;
| | - Farah Asa’ad
- Department of Biomaterials, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, SE-405 30 Göteborg, Sweden;
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Barros SP, Hefni E, Fahimipour F, Kim S, Arora P. Maintaining barrier function of infected gingival epithelial cells by inhibition of DNA methylation. J Periodontol 2020; 91 Suppl 1:S68-S78. [PMID: 32633810 DOI: 10.1002/jper.20-0262] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 06/14/2020] [Accepted: 06/20/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND Infection and inflammation induce epigenetic changes that alter gene expression. In periodontal disease, inflammation, and microbial dysbiosis occur, which can lead to compromised barrier function of the gingival epithelia. Here, we tested the hypotheses that infection of cultured human gingival epithelial (HGEp) cells with Porphyromonas gingivalis disrupts barrier function by inducing epigenetic alterations and that these effects can be blocked by inhibitors of DNA methylation. METHODS Primary HGEp cells were infected with P. gingivalis either in the presence or absence of the non-nucleoside DNA methyltransferase (DNMT) inhibitors RG108, (-) epigallocatechin-3-gallate (EGCG), or curcumin. Barrier function was assessed as transepithelial electrical resistance (TEER). DNA methylation and mRNA abundance were quantified for genes encoding components of three cell-cell junction complexes, CDH1, PKP2, and TJP1. Cell morphology and the abundance of cell-cell junction proteins were evaluated by confocal microscopy. RESULTS Compared to non-infected cells, P. gingivalis infection decreased TEER (P < 0.0001) of HGEp cells; increased methylation of the CDH1, PKP2, and TJP1 (P < 0.0001); and reduced their expression (mRNA abundance) (P < 0.005). Pretreatment with DNMT inhibitors prevented these infection-induced changes in HGEp cells, as well as the altered morphology associated with infection. CONCLUSION Pathogenic infection induced changes in DNA methylation and impaired the barrier function of cultured primary gingival epithelial cells, which suggests a mechanism for systemic consequences of periodontal disease. Inhibition of these events by non-nucleoside DNMT inhibitors represents a potential strategy to treat periodontal disease.
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Affiliation(s)
- Silvana P Barros
- Department of Periodontology, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Eman Hefni
- Department of Periodontology, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Farahnaz Fahimipour
- Department of Periodontology, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Steven Kim
- Department of Periodontology, University of North Carolina at Chapel Hill, Chapel Hill, NC
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Abstract
Periodontitis is a complex disease: (a) various causative factors play a role simultaneously and interact with each other; and (b) the disease is episodic in nature, and bursts of disease activity can be recognized, ie, the disease develops and cycles in a nonlinear fashion. We recognize that various causative factors determine the immune blueprint and, consequently, the immune fitness of a subject. Normally, the host lives in a state of homeostasis or symbiosis with the oral microbiome; however, disturbances in homeostatic balance can occur, because of an aberrant host response (inherited and/or acquired during life). This imbalance results from hyper- or hyporesponsiveness and/or lack of sufficient resolution of inflammation, which in turn is responsible for much of the disease destruction seen in periodontitis. The control of this destruction by anti-inflammatory processes and proresolution processes limits the destruction to the tissues surrounding the teeth. The local inflammatory processes can also become systemic, which in turn affect organs such as the heart. Gingival inflammation also elicits changes in the ecology of the subgingival environment providing optimal conditions for the outgrowth of gram-negative, anaerobic species, which become pathobionts and can propagate periodontal inflammation and can further negatively impact immune fitness. The factors that determine immune fitness are often the same factors that determine the response to the resident biofilm, and are clustered as follows: (a) genetic and epigenetic factors; (b) lifestyle factors, such as smoking, diet, and psychosocial conditions; (c) comorbidities, such as diabetes; and (d) local and dental factors, as well as randomly determined factors (stochasticity). Of critical importance are the pathobionts in a dysbiotic biofilm that drive the viscious cycle. Focusing on genetic factors, currently variants in at least 65 genes have been suggested as being associated with periodontitis based on genome-wide association studies and candidate gene case control studies. These studies have found pleiotropy between periodontitis and cardiovascular diseases. Most of these studies point to potential pathways in the pathogenesis of periodontal disease. Also, most contribute to a small portion of the total risk profile of periodontitis, often limited to specific racial and ethnic groups. To date, 4 genetic loci are shared between atherosclerotic cardiovascular diseases and periodontitis, ie, CDKN2B-AS1(ANRIL), a conserved noncoding element within CAMTA1 upstream of VAMP3, PLG, and a haplotype block at the VAMP8 locus. The shared genes suggest that periodontitis is not causally related to atherosclerotic diseases, but rather both conditions are sequelae of similar (the same?) aberrant inflammatory pathways. In addition to variations in genomic sequences, epigenetic modifications of DNA can affect the genetic blueprint of the host responses. This emerging field will yield new valuable information about susceptibility to periodontitis and subsequent persisting inflammatory reactions in periodontitis. Further studies are required to verify and expand our knowledge base before final cause and effect conclusions about the role of inflammation and genetic factors in periodontitis can be made.
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Affiliation(s)
- Bruno G Loos
- Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Thomas E Van Dyke
- Center for Clinical and Translational Research, Forsyth Institute, Cambridge, Massachusetts, USA
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Fol M, Włodarczyk M, Druszczyńska M. Host Epigenetics in Intracellular Pathogen Infections. Int J Mol Sci 2020; 21:ijms21134573. [PMID: 32605029 PMCID: PMC7369821 DOI: 10.3390/ijms21134573] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 06/23/2020] [Accepted: 06/26/2020] [Indexed: 12/18/2022] Open
Abstract
Some intracellular pathogens are able to avoid the defense mechanisms contributing to host epigenetic modifications. These changes trigger alterations tothe chromatin structure and on the transcriptional level of genes involved in the pathogenesis of many bacterial diseases. In this way, pathogens manipulate the host cell for their own survival. The better understanding of epigenetic consequences in bacterial infection may open the door for designing new vaccine approaches and therapeutic implications. This article characterizes selected intracellular bacterial pathogens, including Mycobacterium spp., Listeria spp., Chlamydia spp., Mycoplasma spp., Rickettsia spp., Legionella spp. and Yersinia spp., which can modulate and reprogram of defense genes in host innate immune cells.
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Affiliation(s)
- Marek Fol
- Correspondence: ; Tel.: +48-42-635-44-72
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Sankaranarayanan R, Saxlin T, Knuuttila M, Ylöstalo P, Suominen AL. Alcohol use and the development of periodontal pockets: An 11‐year follow‐up study. J Periodontol 2020; 91:1621-1631. [DOI: 10.1002/jper.19-0602] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Revised: 02/05/2020] [Accepted: 03/28/2020] [Indexed: 12/25/2022]
Affiliation(s)
| | - Tuomas Saxlin
- Institute of Dentistry University of Eastern Finland Kuopio Finland
- Department of Oral and Maxillofacial Diseases Kuopio University Hospital Kuopio Finland
| | - Matti Knuuttila
- Department of Oral and Maxillofacial Surgery Oulu University Hospital Oulu Finland
| | - Pekka Ylöstalo
- Department of Oral and Maxillofacial Surgery Oulu University Hospital Oulu Finland
- Research Unit of Oral Health Sciences Medical Research Centre Oulu (MRC Oulu) University of Oulu Oulu Finland
| | - Anna Liisa Suominen
- Institute of Dentistry University of Eastern Finland Kuopio Finland
- Department of Oral and Maxillofacial Diseases Kuopio University Hospital Kuopio Finland
- Unit of Public Health Evaluation and Projection National Institute for Health and Welfare (THL ) Helsinki Finland
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Denzer L, Schroten H, Schwerk C. From Gene to Protein-How Bacterial Virulence Factors Manipulate Host Gene Expression During Infection. Int J Mol Sci 2020; 21:ijms21103730. [PMID: 32466312 PMCID: PMC7279228 DOI: 10.3390/ijms21103730] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 05/19/2020] [Accepted: 05/20/2020] [Indexed: 02/06/2023] Open
Abstract
Bacteria evolved many strategies to survive and persist within host cells. Secretion of bacterial effectors enables bacteria not only to enter the host cell but also to manipulate host gene expression to circumvent clearance by the host immune response. Some effectors were also shown to evade the nucleus to manipulate epigenetic processes as well as transcription and mRNA procession and are therefore classified as nucleomodulins. Others were shown to interfere downstream with gene expression at the level of mRNA stability, favoring either mRNA stabilization or mRNA degradation, translation or protein stability, including mechanisms of protein activation and degradation. Finally, manipulation of innate immune signaling and nutrient supply creates a replicative niche that enables bacterial intracellular persistence and survival. In this review, we want to highlight the divergent strategies applied by intracellular bacteria to evade host immune responses through subversion of host gene expression via bacterial effectors. Since these virulence proteins mimic host cell enzymes or own novel enzymatic functions, characterizing their properties could help to understand the complex interactions between host and pathogen during infections. Additionally, these insights could propose potential targets for medical therapy.
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Barros SP, Fahimipour F, Tarran R, Kim S, Scarel-Caminaga RM, Justice A, North K. Epigenetic reprogramming in periodontal disease: Dynamic crosstalk with potential impact in oncogenesis. Periodontol 2000 2020; 82:157-172. [PMID: 31850624 DOI: 10.1111/prd.12322] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Periodontitis is a chronic multifactorial inflammatory disease associated with microbial dysbiosis and characterized by progressive destruction of the periodontal tissues. Such chronic infectious inflammatory disease is recognized as a major public health problem worldwide with measurable impact in systemic health. It has become evident that the periodontal disease phenotypes are not only determined by the microbiome effect, but the extent of the tissue response is also driven by the host genome and epigenome patterns responding to various environmental exposures. More recently there is mounting evidence indicating that epigenetic reprogramming in response to combined intrinsic and environmental exposures, might be particularly relevant due its plasticity and potential application towards precision health. The complex epigenetic crosstalk is reflected in the prognosis and progress of periodontal diseases and may also lead to a favorable landscape for cancer development. This review discusses epigenomics modifications focusing on the role of DNA methylation and pathways linking microbial infection and inflammatory pathways, which are also associated with carcinogenesis. There is a more clear vision whereas 'omics' technologies applied to unveil relevant epigenetic factors could play a significant role in the treatment of periodontal disease in a personalized mode, evidencing that public health approach should coexist with precision individualized treatment.
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Affiliation(s)
- Silvana P Barros
- Department of Periodontology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Farahnaz Fahimipour
- Department of Periodontology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Robert Tarran
- Department of Cell Biology & Physiology, Marsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Steven Kim
- Department of Periodontology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | | | - Anne Justice
- Biomedical and Translational Informatics, Geisinger Health Weis Center for Research, Danville, Pennsylvania, USA
| | - Kari North
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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Emecen-Huja P, Li HF, Ebersole JL, Lambert J, Bush H. Epidemiologic evaluation of Nhanes for environmental Factors and periodontal disease. Sci Rep 2019; 9:8227. [PMID: 31160648 PMCID: PMC6547714 DOI: 10.1038/s41598-019-44445-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Accepted: 04/15/2019] [Indexed: 01/22/2023] Open
Abstract
Periodontitis is a chronic inflammation that destroys periodontal tissues caused by the accumulation of bacterial biofilms that can be affected by environmental factors. This report describes an association study to evaluate the relationship of environmental factors to the expression of periodontitis using the National Health and Nutrition Examination Study (NHANES) from 1999-2004. A wide range of environmental variables (156) were assessed in patients categorized for periodontitis (n = 8884). Multiple statistical approaches were used to explore this dataset and identify environmental variable patterns that enhanced or lowered the prevalence of periodontitis. Our findings indicate an array of environmental variables were different in periodontitis in smokers, former smokers, or non-smokers, with a subset of specific environmental variables identified in each population subset. Discriminating environmental factors included blood levels of lead, phthalates, selected nutrients, and PCBs. Importantly, these factors were found to be coupled with more classical risk factors (i.e. age, gender, race/ethnicity) to create a model that indicated an increased disease prevalence of 2-4 fold across the sample population. Targeted environmental factors are statistically associated with the prevalence of periodontitis. Existing evidence suggests that these may contribute to altered gene expression and biologic processes that enhance inflammatory tissue destruction.
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Affiliation(s)
- P Emecen-Huja
- Division of Periodontics, College of Dental Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
| | - H-F Li
- Providence St. Joseph Health of Oregon, Medical Data and Research Center, Portland, OR, USA
| | - J L Ebersole
- School of Dental Medicine, University of Nevada, Las Vegas, Las Vegas, Nevada, USA
| | - J Lambert
- College of Nursing, University of Cincinnati, Cincinnati, OH, USA
| | - H Bush
- Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY, USA
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Nagarajan R, Miller CS, Dawson D, Ebersole JL. Biologic modelling of periodontal disease progression. J Clin Periodontol 2019; 46:160-169. [DOI: 10.1111/jcpe.13064] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Revised: 12/03/2018] [Accepted: 01/05/2019] [Indexed: 12/17/2022]
Affiliation(s)
- Radhakrishnan Nagarajan
- Division of Biomedical Informatics College of Medicine University of Kentucky Lexington Kentucky
| | - Craig S. Miller
- Division of Oral Diagnosis, Oral Medicine and Oral Radiology University of Kentucky Lexington Kentucky
- Center for Oral Health Research College of Dentistry University of Kentucky Lexington Kentucky
| | - Dolph Dawson
- Center for Oral Health Research College of Dentistry University of Kentucky Lexington Kentucky
- Division of Periodontics University of Kentucky Lexington Kentucky
| | - Jeffrey L. Ebersole
- Center for Oral Health Research College of Dentistry University of Kentucky Lexington Kentucky
- Department of Biomedical Sciences School of Dental Medicine University of Nevada Las Vegas Las Vegas Nevada
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Ebersole JL, Lambert J, Bush H, Huja PE, Basu A. Serum Nutrient Levels and Aging Effects on Periodontitis. Nutrients 2018; 10:E1986. [PMID: 30558282 PMCID: PMC6316450 DOI: 10.3390/nu10121986] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 12/06/2018] [Accepted: 12/12/2018] [Indexed: 12/12/2022] Open
Abstract
Periodontal disease damages tissues as a result of dysregulated host responses against the chronic bacterial biofilm insult and approximately 50% of US adults >30 years old exhibit periodontitis. The association of five blood nutrients and periodontitis were evaluated due to our previous findings regarding a potential protective effect for these nutrients in periodontal disease derived from the US population sampled as part of the National Health and Nutrition Examination Survey (1999⁻2004). Data from over 15,000 subjects was analyzed for blood levels of cis-β-carotene, β-cryptoxanthin, folate, vitamin D, and vitamin E, linked with analysis of the presence and severity of periodontitis. Moderate/severe disease patients had lower cis-β-carotene levels across all racial/ethnic groups and these decreased levels in moderate/severe periodontitis were exacerbated with age. β-cryptoxanthin demonstrated lower levels in severe disease patients across the entire age range in all racial/ethnic groups. Folate differences were evident across the various age groups with consistently lower levels in periodontitis patients >30 years and most pronounced in females. Lower levels of vitamin D were consistently noted across the entire age range of patients with a greater difference seen in females with periodontitis. Finally, an analytical approach to identify interactions among these nutrients related to age and periodontitis showed interactions of vitamin D in females, and folate with race in the population. These findings suggest that improving specific nutrient intake leading to elevated blood levels of a combination of these protective factors may provide a novel strategy to affect the significant increase in periodontitis that occurs with aging.
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Affiliation(s)
- Jeffrey L Ebersole
- Department of Biomedical Sciences, School of Dental Medicine, University of Nevada Las Vegas, 1001 Shadow Lane, B221, MS 7425, Las Vegas, NV 89106, USA.
| | - Joshua Lambert
- College of Nursing, University of Cincinnati; Cincinnati, OH 45221, USA.
| | - Heather Bush
- Department of Biostatistics, College of Public Health, University of Kentucky; Lexington, KY 40536, USA.
| | - Pinar Emecen Huja
- Department of Periodontics, School of Dentistry, Medical University of South Carolina; Charleston, SC 29425, USA.
| | - Arpita Basu
- Department of Kinesiology and Nutrition Sciences, School of Allied Health Sciences, University of Nevada Las Vegas, Las Vegas, NV 89106, USA.
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Yu N, Yang J, Mishina Y, Giannobile WV. Genome Editing: A New Horizon for Oral and Craniofacial Research. J Dent Res 2018; 98:36-45. [PMID: 30354846 DOI: 10.1177/0022034518805978] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Precise and efficient genetic manipulations have enabled researchers to understand gene functions in disease and development, providing a platform to search for molecular cures. Over the past decade, the unprecedented advancement of genome editing techniques has revolutionized the biological research fields. Early genome editing strategies involved many naturally occurring nucleases, including meganucleases, zinc finger nucleases, and transcription activator-like effector-based nucleases. More recently, the clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR-associated nucleases (CRISPR/Cas) system has greatly enriched genetic manipulation methods in conducting research. Those nucleases generate double-strand breaks in the target gene sequences and then utilize DNA repair mechanisms to permit precise yet versatile genetic manipulations. The oral and craniofacial field harbors a plethora of diseases and developmental defects that require genetic models that can exploit these genome editing techniques. This review provides an overview of the genome editing techniques, particularly the CRISPR/Cas9 technique, for the oral and craniofacial research community. We also discuss the details about the emerging applications of genome editing in oral and craniofacial biology.
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Affiliation(s)
- N Yu
- 1 Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA
| | - J Yang
- 2 Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.,3 The State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory for Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Y Mishina
- 2 Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI, USA
| | - W V Giannobile
- 1 Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.,4 Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, MI, USA
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Zhao B, Li X, Li R. Genetic Relationship Between IL-6 rs1800796 Polymorphism and Susceptibility to Periodontitis. Immunol Invest 2018; 48:268-282. [PMID: 30300034 DOI: 10.1080/08820139.2018.1517365] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
BACKGROUND There are accumulating reports for the potential role of Interleukin-6 (IL-6) rs1800796 polymorphism in the risk of periodontitis. However, distinct conclusions are observed. In this study, we have an interest in comprehensively analyzing the genetic relationship between IL-6 rs1800796 and the susceptibility to periodontitis. METHODS We retrieved the eligible case-control studies from on-line database and conducted a meta-analysis. P-value of association test, OR (odd ratios) and 95% CI (confidence interval) were calculated for the assessment of potential genetic association. RESULTS We enrolled a total of 20 case-control studies for pooling analysis. A positive association between periodontitis cases and controls was observed in the overall meta-analysis under all genetic models (all P < 0.05, OR > 1). Similar results were detected in the "population-based, PB" and "China" subgroups (all P < 0.05, OR > 1). In the "Asian" subgroup, there is an increased periodontitis risk under the allele, homozygote, heterozygote, dominant and carrier models (all P < 0.05, OR > 1). Nevertheless, negative results were found in the "Caucasian" subgroup under all models [all P > 0.05]. In addition, a positive association between IL-6 rs1800796 and the risk of chronic periodontitis was detected under the models of allele [G vs. C], GG vs. CC, GG vs. CC+ CG and carrier [G vs. C] (all P < 0.05, OR > 1). CONCLUSION IL-6 rs1800796 may serve as one genetic risk factor for periodontitis patients in the Asian population, especially the Chinese population. G/G genotype of IL-6 rs1800796 appears to be associated with an increased risk of chronic periodontitis.
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Affiliation(s)
- Bo Zhao
- a Dental Department , Tianjin First Center Hospital , Tianjin , People's Republic of China
| | - Xiaoqian Li
- a Dental Department , Tianjin First Center Hospital , Tianjin , People's Republic of China
| | - Ronghua Li
- a Dental Department , Tianjin First Center Hospital , Tianjin , People's Republic of China
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Bevilacqua L, Navarra CO, Pirastu N, Lenarda RD, Gasparini P, Robino A. A genome-wide association study identifies an association between variants in EFCAB4B gene and periodontal disease in an Italian isolated population. J Periodontal Res 2018; 53:992-998. [PMID: 30284742 DOI: 10.1111/jre.12598] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Revised: 06/04/2018] [Accepted: 07/12/2018] [Indexed: 01/23/2023]
Abstract
BACKGROUND AND OBJECTIVE Periodontitis in one of the most prevalent dental diseases. Despite numerous studies have investigated its aetiopathogenetic factors, few works have focused on its genetic predisposition and most of them took into account only candidate genes. Therefore, we conducted a Genome Wide Association Study in an Italian isolated population aimed at uncovering genetic variants that predispose to this disorder. METHODS Diagnosis of chronic periodontitis was made following the criteria of the American Academy of Periodontology. Patients with chronic periodontitis were grouped into different categories: slight, severe, localized and generalized. A control group composed by people without signs of periodontitis or gingivitis was defined. DNA was genotyped using 370k Illumina chips. Linear mixed model regression was used to test the association between each single nucleotide polymorphism (SNP) (independent variable) and the periodontitis status (dependent variable), controlling for confounders sex, age and smoking. The genomic kinship matrix was also used as random effect. RESULTS Four SNPs on the gene EFCAB4B resulted significantly associated to localized periodontitis (P < 5 × 10-8 ), with the best hit on the rs242016 SNP (P = 1.5 × 10-8 ). CONCLUSION We have identified a novel significant association between the EFCAB4B gene and localized periodontitis. These results open a new perspective in the understanding of genetic factors contributing to this common disorder.
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Affiliation(s)
| | - Chiara O Navarra
- Department of Medical Sciences, University of Trieste, Trieste, Italy
| | - Nicola Pirastu
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
| | | | - Paolo Gasparini
- Department of Medical Sciences, University of Trieste, Trieste, Italy.,Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, Italy
| | - Antonietta Robino
- Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, Italy
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Ryder MI, Couch ET, Chaffee BW. Personalized periodontal treatment for the tobacco- and alcohol-using patient. Periodontol 2000 2018; 78:30-46. [PMID: 30198132 PMCID: PMC6132065 DOI: 10.1111/prd.12229] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The use of various forms of tobacco is one of the most important preventable risk factors for the incidence and progression of periodontal disease. Tobacco use negatively affects treatment outcomes for both periodontal diseases and conditions, and for dental implants. Tobacco-cessation programs can mitigate these adverse dental treatment outcomes and may be the most effective component of a personalized periodontal treatment approach. In addition, heavy alcohol consumption may exacerbate the adverse effects of tobacco use. In this review, the microbiology, host/inflammatory responses and genetic characteristics of the tobacco-using patient are presented as a framework to aid the practitioner in developing personalized treatment strategies for these patients. These personalized approaches can be used for patients who use a variety of tobacco products, including cigarettes, cigars, pipes, smokeless tobacco products, e-cigarettes and other tobacco forms, as well as patients who consume large amounts of alcohol. In addition, principles for developing personalized tobacco-cessation programs, using both traditional and newer motivational and pharmacological approaches, are presented.
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Affiliation(s)
- Mark I Ryder
- Department of Orofacial Sciences, School of Dentistry, University of California, San Francisco, CA, USA
| | - Elizabeth T Couch
- Department or Preventive and Restorative Sciences, School of Dentistry, University of California, San Francisco, CA, USA
| | - Benjamin W Chaffee
- Department or Preventive and Restorative Sciences, School of Dentistry, University of California, San Francisco, CA, USA
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Peyyala R, Emecen-Huja P, Ebersole JL. Environmental lead effects on gene expression in oral epithelial cells. J Periodontal Res 2018; 53:961-971. [PMID: 30152021 DOI: 10.1111/jre.12594] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Revised: 06/20/2018] [Accepted: 07/04/2018] [Indexed: 01/02/2023]
Abstract
BACKGROUND AND OBJECTIVE Host responses in periodontitis span a range of local and emigrating cell types and biomolecules. Accumulating evidence regarding the expression of this disease across the population suggests some component of genetic variation that controls onset and severity of disease, in concert with the qualitative and quantitative parameters of the oral microbiome at sites of disease. However, there remains little information regarding the capacity of accruing environmental stressors or modifiers over a lifespan at both the host genetic and microbial ecology levels to understand fully the population variation in disease. This study evaluated the impact of environmental lead exposure on the responses of oral epithelial cells to challenge with a model pathogenic oral biofilm. METHODS AND RESULTS Using NanoString technology to quantify gene expression profiles of an array of 511 host response-associated genes in the epithelial cells, we identified an interesting primary panel of basal responses of the cells with numerous genes not previously considered as major response markers for epithelial cells, eg, interleukin (IL)-32, CTNNB1, CD59, MIF, CD44 and CD99. Even high levels of environment lead had little effect on these constitutive responses. Challenge of the cells with the biofilms (Streptococcus gordonii/Fusobacterium nucleatum/Porphyromonas gingivalis) resulted in significant increases in an array of host immune-related genes (134 of 511). The greatest magnitude in differential expression was observed with many genes not previously described as major response genes in epithelial cells, including IL-32, CD44, NFKBIA, CTSC, TNFAIP3, IL-1A, IL-1B, IL-8 and CCL20. The effects of environmental lead on responses to the biofilms were mixed, although levels of IL-8, CCL20 and CD70 were significantly decreased at lead concentrations of 1 and/or 5 μmol/L. CONCLUSION The results provided new information on a portfolio of genes expressed by oral epithelial cells, targeted substantial increases in an array of immune-related genes post-biofilm challenge, and a focused impact of environmental lead on these induced responses.
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Affiliation(s)
- Rebecca Peyyala
- Center for Oral Health Research and Division of Periodontology, College of Dentistry, University of Kentucky, Lexington, Kentucky
| | - Pinar Emecen-Huja
- Center for Oral Health Research and Division of Periodontology, College of Dentistry, University of Kentucky, Lexington, Kentucky
| | - Jeffrey L Ebersole
- Center for Oral Health Research and Division of Periodontology, College of Dentistry, University of Kentucky, Lexington, Kentucky
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