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Wang Y, Zhu J, Zhou Y, Tang Y, Huang C. Exploring Relationships Between Circulating Interleukins and Pulp and Periapical Diseases: A Bidirectional Mendelian Randomization Study. J Endod 2025; 51:132-139. [PMID: 39580142 DOI: 10.1016/j.joen.2024.11.010] [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: 06/27/2024] [Revised: 11/16/2024] [Accepted: 11/17/2024] [Indexed: 11/25/2024]
Abstract
INTRODUCTION The aim of this study was to comprehensively evaluate the links of genetic predisposition among 13 common circulating interleukins (ILs) and endodontic diseases by using a 2-sample Mendelian randomization method. METHODS Single nucleotide polymorphisms were chosen as instrumental variables from summary data of genome-wide association studies (GWASs), using the inverse-variance-weighted method as the primary analysis. In addition, a variety of sensitivity analyses was conducted to evaluate the resilience of the primary outcomes and identify any inherent pleiotropic effects. RESULTS After multiple comparison corrections, 4 circulating ILs were genetically predicted to significantly play a role in endodontic diseases. Among these, circulating IL-17 (odds ratio [OR]IVW, 1.33; 95% confidence interval [CI], 1.15-1.54; P < 3.85 × 10-3) were significantly identified as potential risk-increasing factors toward pulp and periapical diseases, and circulating IL-16 (ORIVW, 0.89; 95% CI, 0.83 to 0.94; P < 3.85 × 10-3) may exert protective effects on the development of periapical abscess. In the reverse analyses, null significantly association was found between genetic liability to endodontics disorders and the corresponding circulating inflammatory biomarkers. Overall, sensitivity analyses were consistent with the estimates direction of primary analyses results, supporting the reliability of findings. CONCLUSIONS Given the unavoidable limitations presented in this study, our findings provided significant evidence to support the identification of elevated IL-16 levels as a potential risk-mitigating factor, whereas elevated IL-17 levels exhibit potentially deleterious effects on endodontic disorders. Future validation is warranted to examine the conclusions of our study and to evaluate the potential application of these circulating ILs as lifestyle or pharmacological targets for oral health care.
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Affiliation(s)
- Yuqiang Wang
- State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Jiakang Zhu
- State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Yueli Zhou
- State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Ying Tang
- State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
| | - Cui Huang
- State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
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Falatah AM, Alturki SA, Aldahami AI, Alrashidi NA, Sinnah Y, Aldgeel RM, Alanazi KZ, Alkhaled AS, ALjuaid TS, Alotaibi NH, Altwijri WJ. Exploring the Influence of Genetic Single-Nucleotide Polymorphism (SNPs) on Endodontic Pathologies: A Comprehensive Review. Cureus 2024; 16:e74389. [PMID: 39723289 PMCID: PMC11669393 DOI: 10.7759/cureus.74389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/24/2024] [Indexed: 12/28/2024] Open
Abstract
A considerable portion of the global population is affected by pulpitis and periapical lesions. While the impact of infections caused by various microbes and host effector molecules in pulpal and periapical diseases is widely recognized, disease susceptibility and progression are also influenced by the dynamic interaction between host genetic factors and environmental influences. Apical periodontitis occurs as an inflammatory response to microorganisms present in the root canals of infected teeth. Initially functioning as the body's defense mechanism, this response often progresses to chronic inflammation. Several studies have established associations between genetic polymorphisms and various dental conditions, including temporomandibular joint (TMJ) disorders, dental caries, orthognathic surgeries, open bite malocclusion, periapical periodontitis, pulp stones, pulpitis, periapical abscesses, local anesthesia complications, and endodontic treatment outcomes. Key findings from this review highlight the role of specific single-nucleotide polymorphisms (SNPs) in genes such as matrix metalloproteinase (MMP)1, MMP2, MMP3, interleukin (IL)-1β, IL-6, IL-17, and tumor necrosis factor-alpha (TNF-α), which influence inflammatory pathways and tissue remodeling. For example, SNPs in interleukin genes, such as IL-1β (-511 C/T), have been linked to an increased risk of apical periodontitis, while MMP gene polymorphisms contribute to tissue degradation in periapical lesions. This review underscores the importance of identifying genetic markers that drive disease progression and inflammatory processes in pulpal and periapical pathologies. A better understanding of these mechanisms can inform strategies for disease prevention, personalized treatment approaches, and improved endodontic outcomes.
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Affiliation(s)
| | | | - Abdulatif I Aldahami
- Dentistry, Qassim University, Bachelor Degree of Dental Surgery (BDS), Buraydah, SAU
| | | | | | | | | | - Amira S Alkhaled
- College of Dentistry, King Saud bin Abdulaziz University for Health Sciences, Riyadh, SAU
| | | | | | - Worod J Altwijri
- Dentistry, Princess Nourah Bint Abdulrahman University, Riyadh, SAU
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Jain S, Sundar S, Haritha JS, Natanasabapathy V. Comparision of interleukin-1β concentrations in posttreatment endodontic disease and other pulpal and periapical conditions - A clinical study. JOURNAL OF CONSERVATIVE DENTISTRY AND ENDODONTICS 2024; 27:843-848. [PMID: 39372575 PMCID: PMC11451682 DOI: 10.4103/jcde.jcde_324_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 06/24/2024] [Accepted: 06/27/2024] [Indexed: 10/08/2024]
Abstract
Aim To evaluate interleukin (IL)-1β concentrations in periapical tissue fluid (PTF) in persistent apical periodontitis requiring endodontic retreatment and to compare the levels of IL-1β with chronic apical periodontitis, symptomatic irreversible pulpitis (SIP), normal pulpal, and periapical tissues. Materials and Methods The patients were selected based on inclusion and exclusion criteria and divided into 4 groups based on the pulpal and periapical status: Posttreatment endodontic diseases (PTED): Teeth with PTED due to failed primary root canal treatment having periapical radiolucency. PNAP: Teeth requiring root canal treatment due to pulpal necrosis having periapical radiolucency. SIP: Teeth with symptoms of SIP with healthy periapical tissues). Intentional root canal treatment (IRCT): Teeth requiring IRCT (healthy pulp and periapical tissues). The access cavity was redefined and the preexisting filling was removed using H-files. The root canals were minimally enlarged followed by collection of PTF using paper points, in the case of group PTED. For groups PNAP, SIP, and IRCT, conventional access cavity preparation was done followed by enlargement of canals till 20, 0.02. PTF was collected using 15, 0.02 size absorbent points 2 mm beyond the apex. Levels of IL-1β was assessed by enzyme-linked immunosorbent assay. Results A statistically significant difference was seen in levels of IL-1β in all the groups. The highest concentration was seen in group PTED (85.07 ± 11.57 pg/mL) followed by group PNAP (37.60 ± 10.94 pg/mL), group SIP (8.40 ± 1.99 pg/mL), and the least was seen in group IRCT (3.47 ± 1.36 pg/mL). Conclusion The levels of IL-1β were highest in PETD cases followed by PNAP, SIP, and IRCT. This indicates the severity of inflammation in PETD cases as compared to other endodontic diseases.
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Affiliation(s)
- Shivangi Jain
- Department of Conservative Dentistry and Endodontics, Meenakshi Ammal Dental College, Chennai, Tamil Nadu, India
| | - Sathish Sundar
- Department of Conservative Dentistry and Endodontics, Meenakshi Ammal Dental College, Chennai, Tamil Nadu, India
| | - J. S. Haritha
- Department of Conservative Dentistry and Endodontics, Meenakshi Ammal Dental College, Chennai, Tamil Nadu, India
| | - Velmurugan Natanasabapathy
- Department of Conservative Dentistry and Endodontics, Meenakshi Ammal Dental College, Chennai, Tamil Nadu, India
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Baris SD, Turkyilmaz A, Derici MK. Effects of Nd: YAG laser on tumour necrosis factor-alpha, interleukin-1beta and interferon-gamma levels in teeth with apical periodontitis: A clinical study. AUST ENDOD J 2023; 49:657-664. [PMID: 37746745 DOI: 10.1111/aej.12799] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 07/20/2023] [Accepted: 09/08/2023] [Indexed: 09/26/2023]
Abstract
This study aimed to evaluate the levels of tumour necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interferon-gamma (IFN-γ) with asymptomatic apical periodontitis (AP). A total of 60 participants were randomly divided into two groups: the conventional irrigation (control) and the Nd: YAG laser irradiation. The interstitial fluids were obtained after root canal cleaning (day 0) and 1 week later (day 7). The TNF-α, IL-1β and IFN-γ levels were assayed using the enzyme-linked immunosorbent assay. The Mann-Whitney U, continuity correction chi-square, Pearson chi-square and Fisher exact tests were used. An increased level of cytokines on day 7 in the control group was observed, without statistically significant differences (p > 0.05). All cytokine levels decreased over time in the laser group. Only the IL-1β level showed a significant difference (p < 0.05). Nd: YAG irradiation has a positive effect on decreasing the proinflammatory cytokine level and may help to control infection in teeth with AP.
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Affiliation(s)
- Sevda Durust Baris
- Department of Endodontics, Faculty of Dentistry, Kirikkale University, Kirikkale, Turkey
| | - Ali Turkyilmaz
- Department of Endodontics, Faculty of Dentistry, Kirikkale University, Kirikkale, Turkey
| | - Mehmet Kursat Derici
- Department of Medical Pharmacology, Gulhane Faculty of Medicine, University of Health Science, Ankara, Turkey
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Virdee SS, Bashir NZ, Krstic M, Camilleri J, Grant MM, Cooper PR, Tomson PL. Periradicular tissue fluid-derived biomarkers for apical periodontitis: An in vitro methodological and in vivo cross-sectional study. Int Endod J 2023; 56:1222-1240. [PMID: 37464545 DOI: 10.1111/iej.13956] [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: 03/15/2023] [Revised: 07/04/2023] [Accepted: 07/14/2023] [Indexed: 07/20/2023]
Abstract
BACKGROUND Periradicular tissue fluid (PTF) offers a source of diagnostic, prognostic and predictive biomarkers for endodontic disease. AIMS (1) To optimize basic parameters for PTF paper point sampling in vitro for subsequent in vivo application. (2) To compare proteomes of PTF from teeth with normal apical tissues (NAT) and asymptomatic apical periodontitis (AAP) using high-throughput panels. METHODOLOGY (1) To assess volume absorbance, paper points (n = 20) of multiple brands, sizes and sampling durations were inserted into PBS/1%BSA at several depths. Wetted lengths (mm) were measured against standard curves to determine volume absorbance (μL). To assess analyte recovery, paper points (n = 6) loaded with 2 μL recombinant IL-1β (15.6 ng/mL) were eluted into 250 μL: (i) PBS; (ii) PBS/1% BSA; (iii) PBS/0.1% Tween20; (iv) PBS/0.25 M NaCl. These then underwent: (i) vortexing; (ii) vortexing/centrifugation; (iii) centrifugation; (iv) incubation/vortexing/centrifugation. Sandwich-ELISAs determined analyte recovery (%) against positive controls. (2) Using optimized protocols, PTF was retrieved from permanent teeth with NAT or AAP after accessing root canals. Samples, normalized to total fluid volume (TFV), were analysed to determine proteomic profiles (pg/TFV) of NAT and AAP via O-link Target-48 panel. Correlations between AAP and diagnostic accuracy were explored using principal-component analysis (PCA) and area under receive-operating-characteristic curves (AUC [95% CI]), respectively. Statistical comparisons were made using Mann-Whitney U, anova and post hoc Bonferonni tests (α < .01). RESULTS (1) UnoDent's 'Classic' points facilitated maximum volume absorbance (p < .05), with no significant differences after 60 s (1.6 μL [1.30-1.73]), 1 mm depth and up to 40/0.02 (2.2 μL [1.98-2.20]). For elution, vortexing (89.3%) and PBS/1% BSA (86.9%) yielded the largest IL-1β recovery (p < .05). (2) 41 (NAT: 13; AAP: 31) PTF samples proceeded to analysis. The panel detected 18 analytes (CCL-2, -3, -4; CSF-1; CXCL-8, -9; HGF; IL-1β, -6, -17A, -18; MMP-1, -12; OLR-1; OSM; TNFSF-10, -12; VEGF-A) in ≥75% of AAP samples at statistically higher concentrations (p < .01). CXCL-8, IL-1β, OLR-1, OSM and TNFSF-12 were strongly correlated to AAP. 'Excellent' diagnostic performance was observed for TNFSF-12 (AUC: 0.94 [95% CI: 0.86-1.00]) and the PCA-derived cluster (AUC: 0.96 [95% CI: 0.89-1.00]). CONCLUSIONS Optimized PTF sampling parameters were identified in this study. When applied clinically, high-throughput proteomic analyses revealed complex interconnected networks of potential biomarkers. TNFSF-12 discriminated periradicular disease from health the greatest; however, clustering analytes further improved diagnostic accuracy. Additional independent investigations are required to validate these findings.
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Affiliation(s)
- Satnam S Virdee
- Institute of Clinical Sciences, School of Dentistry & Birmingham Dental Hospital, University of Birmingham, Birmingham, UK
| | | | - Milan Krstic
- Institute of Clinical Sciences, School of Dentistry & Birmingham Dental Hospital, University of Birmingham, Birmingham, UK
| | - Josette Camilleri
- Institute of Clinical Sciences, School of Dentistry & Birmingham Dental Hospital, University of Birmingham, Birmingham, UK
| | - Melissa M Grant
- Institute of Clinical Sciences, School of Dentistry & Birmingham Dental Hospital, University of Birmingham, Birmingham, UK
| | - Paul R Cooper
- Department of Oral Sciences, Faculty of Dentistry, University of Otago, Dunedin, New Zealand
| | - Phillip L Tomson
- Institute of Clinical Sciences, School of Dentistry & Birmingham Dental Hospital, University of Birmingham, Birmingham, UK
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Khoshbin E, Salehi R, Behroozi R, Sadr S, Zamani A, Farhadian M, Karkehabadi H. The effect of low-dose aspirin on aspirin triggered lipoxin, interleukin 1 beta, and prostaglandin E2 levels in periapical fluid: a double-blind randomized clinical trial. BMC Oral Health 2023; 23:530. [PMID: 37525211 PMCID: PMC10388445 DOI: 10.1186/s12903-023-03243-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 07/19/2023] [Indexed: 08/02/2023] Open
Abstract
BACKGROUND The role of pro-resolving mediators in inflammation is a new concern in research. The effect of low-dose aspirin on production of a special kind of these mediators named aspirin triggered lipoxin (ATL) has been studied on different tissues. This randomized clinical trial evaluated the effect of low-dose aspirin on ATL and pro-inflammatory mediators' level in periapical fluid of necrotic teeth with large lesions. METHODS Twenty-four patients with necrotic pulp and periapical lesion were randomly assigned to low-dose aspirin and placebo groups. In the first appointment, canals were shaped up to F3 size and #40 K-file and cleaned with 10 milliliters 2.5% sodium hypochlorite and 17% Ethylenediaminetetraacetic acid. Periapical fluid was sampled by a paper cone. The tooth was temporized without any intracanal medication. Tablets were administered for 7 days, then the teeth were re-opened and the sampling were repeated. Interleukin-1 beta (IL-1β), prostaglandin E2 (PGE2) and ATL were analyzed by enzyme-linked immunosorbent assay. Data were analyzed with paired t-test using SPSS statistical software, version 21 (α = 0.05). RESULTS A significant reduction in PGE2 and IL-1β was noted in the aspirin-treated group while an increase in ATL was observed (P < 0.001). There was no significant difference in the mediator scores before and after in the placebo-treated group (P > 0.05). CONCLUSION Low-dose aspirin can influence the inflammatory process by reducing pro-inflammatory mediators such as PGE2 and IL-1β, as well as increasing the pro-resolving mediators such as ATL. TRIAL REGISTRATION IRCT20191211045702N1.
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Affiliation(s)
- Elham Khoshbin
- Department of Endodontics, Dental School, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Razieh Salehi
- Department of Endodontics, Dental School, Hamadan University of Medical Sciences, Hamadan, Iran
- Department of Endodontics, School of dentistry, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Rooholah Behroozi
- Department of Endodontics, Dental School, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Soroush Sadr
- Department of Endodontics, Dental School, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Alireza Zamani
- Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Maryam Farhadian
- Department of Biostatistics, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Hamed Karkehabadi
- Department of Endodontics, Dental School, Hamadan University of Medical Sciences, Hamadan, Iran.
- Department of Endodontics, Dental Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
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Liu Y, Wang Y, Zhang X, Jiao Y, Duan L, Dai L, Yan H. Chronic acrylamide exposure resulted in dopaminergic neuron loss, neuroinflammation and motor impairment in rats. Toxicol Appl Pharmacol 2022; 451:116190. [PMID: 35917840 DOI: 10.1016/j.taap.2022.116190] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 07/13/2022] [Accepted: 07/27/2022] [Indexed: 11/26/2022]
Abstract
Acrylamide (ACR) as a by-product of Maillard reaction is widely present in food. Although ACR is known to exhibit neurotoxicity, most studies about ACR neurotoxicity are currently short-term high-dose providing limited reference value for human exposure. The present study aims to determine the effects of chronic ACR exposure on dopaminergic neurons in rat nigra and the potential mechanism from the perspective of NLRP3 inflammasome-mediated neuroinflammation. The SD rats were maintained on treated drinking water providing dosages of 0, 0.5, or 5 mg/kg/day ACR for 12 months. ACR exposure caused motor dysfunction in rats, which was associated with dopaminergic neuron loss, α-Synuclein (α-Syn) accumulation and decreased brain-derived neurotrophic factor (BDNF) in nigra. ACR activated microglia by increasing Iba-1+, Iba-1+CD68+ positive cells and the percentage of ameboid-shaped ones in rat nigra. ACR markedly upregulated the protein levels of NLRP3 inflammasome constituents NLRP3 and caspase-1 and inflammatory cytokine IL-1β. ACR chronic exposure increased the risk of Parkinson's disease (PD) like dopaminergic neuron depletion in nigra potentially through NLRP3 inflammasome-mediated neuroinflammtion.
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Affiliation(s)
- Ying Liu
- Department of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong-Road, Wuhan 430030, PR China; Department of Clinical Laboratory, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, PR China
| | - Yiqi Wang
- Department of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong-Road, Wuhan 430030, PR China
| | - Xing Zhang
- Department of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong-Road, Wuhan 430030, PR China
| | - Yang Jiao
- Department of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong-Road, Wuhan 430030, PR China
| | - Lian Duan
- Department of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong-Road, Wuhan 430030, PR China
| | - Lingling Dai
- Experimental Teaching Center of Preventive Medicine School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, PR China
| | - Hong Yan
- Department of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong-Road, Wuhan 430030, PR China.
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Petean IBF, Silva-Sousa AC, Cronenbold TJ, Mazzi-Chaves JF, Silva LABD, Segato RAB, Castro GAPD, Kuchler EC, Paula-Silva FWG, Damião Sousa-Neto M. Genetic, Cellular and Molecular Aspects involved in Apical Periodontitis. Braz Dent J 2022; 33:1-11. [PMID: 36043561 PMCID: PMC9645190 DOI: 10.1590/0103-6440202205113] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 08/03/2022] [Indexed: 11/26/2022] Open
Abstract
The development, establishment and repair of apical periodontitis (AP) is
dependent of several factors, which include host susceptibility, microbial
infection, immune response, quality of root canal treatment and organism's
ability to repair. The understanding of genetic contributions to the risk of
developing AP and presenting persistent AP has been extensively explored in
modern Endodontics. Thus, this article aims to provide a review of the
literature regarding the biochemical mediators involved in immune response
signaling, osteoclastogenesis and bone neoformation, as the genetic components
involved in the development and repair of AP. A narrative review of the
literature was performed through a PUBMED/MEDLINE search and a hand search of
the major AP textbooks. The knowledge regarding the cells, receptors and
molecules involved in the host's immune-inflammatory response during the
progression of AP added to the knowledge of bone biology allows the
identification of factors inherent to the host that can interfere both in the
progression and in the repair of these lesions. The main outcomes of studies
evaluated in the review that investigated the correlation between genetic
polymorphisms and AP in the last five years, demonstrate that genetic factors of
the individual are involved in the success of root canal treatment. The
discussion of this review gives subsides that may help to glimpse the
development of new therapies based on the identification of therapeutic targets
and the development of materials and techniques aimed at acting at the molecular
level for clinical, radiographic and histological success of root canal
treatment.
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Affiliation(s)
- Igor Bassi Ferreira Petean
- Department of Restorative Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Brazil
| | - Alice Corrêa Silva-Sousa
- Department of Restorative Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Brazil
| | | | | | - Lea Assed Bezerra da Silva
- Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Raquel Assed Bezerra Segato
- Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | | | - Erika Calvano Kuchler
- Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.,Department of Orthodontics, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany
| | | | - Manoel Damião Sousa-Neto
- Department of Restorative Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Brazil
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Comparative effects of concentrated growth factors on the biological characteristics of periodontal ligament cells and stem cells from apical papilla. J Endod 2022; 48:1029-1037. [DOI: 10.1016/j.joen.2022.05.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 03/30/2022] [Accepted: 05/01/2022] [Indexed: 12/14/2022]
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Local immunomodulatory effects of intracanal medications in apical periodontitis. J Endod 2022; 48:430-456. [PMID: 35032538 DOI: 10.1016/j.joen.2022.01.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 12/31/2021] [Accepted: 01/03/2022] [Indexed: 12/11/2022]
Abstract
The immune system is an extremely complex biological network that plays a crucial role in the hemostasis of periapical tissue, pathogenesis of apical periodontitis (AP) as well as periapical tissue healing. The successful elimination of microbial infections remains a significant challenge, mostly due to the ever-growing development of antimicrobial-resistant pathogens. The bacterial endurance in the root canal system contributes to features ranging from altered post-treatment healing to exacerbation of chronic periradicular immune response, that compromise the outcome of endodontic treatment. A highly effective strategy for combating infectious diseases and the associated inflammation-mediated tissue damage is to modulate the host immune response in conjunction with antimicrobial therapy. There are several medications currently used in endodontic treatment, however, they suffer various levels of microbial resistance and do not deliver all the required characteristics to simultaneously address both intracanal bacteria and periapical inflammation. Interaction of antimicrobial agents with the immune system can impact its function, leading to immune-suppressive or immune-stimulatory effects. The group of non-conventional antimicrobial medications, such as antimicrobial peptides, propolis, and nanomaterials, are agents that provide strong antimicrobial effectiveness and concomitant immunomodulatory and/or reparative effect, without any host tissue damages. Herein, we provide an overview of local immune modulation in AP and a comprehensive review of the immunomodulatory effect of antimicrobials intracanal medications applied in endodontics with specific emphasis on the antimicrobial nanomaterial-based approaches that provide immunomodulatory potential for successful clinical deployment in endodontics.
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Da Silva RAB, Da Silva LAB, Gabriel-Junior EA, Sorgi CA, Faccioli LH, Massoni VV, Nelson-Filho P, Pucinelli CM. M1 and M2 macrophages phenotypes modulation after stimuli with materials used in endodontic treatment. Braz Dent J 2021; 32:32-43. [PMID: 34755788 DOI: 10.1590/0103-6440202104038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 03/20/2021] [Indexed: 11/21/2022] Open
Abstract
The aim of this study was to evaluate the M1 and M2 macrophage modulation after stimuli with different materials used during endodontic treatment. In bone marrow-derived macrophage cell culture, from males C57BL/6 wild-type (WT) mice, gene expression analysis of markers to M1 and M2 macrophages was performed by qRT-PCR (Cxcl10, CxCL9, iNOS, Arg1, Chil3, Retnla and MRC1) and cytokine quantification by Luminex® (GM-CSF, IL-10, IL-6, IL-1β and TNF-α) after exposure to the five endodontic sealers: AH Plus, Sealapex Xpress, Endosequence BC Sealer, BioRoot RCS and a calcium hydroxide-based paste. For normal values, ANOVA test was used, followed by Tukey post-test. For non-normal values, the Kruskall-Wallis test was used. BioRootTM RCS and EndoSequence BC SealerTM stimulated the highest expression of markers for M1 macrophages, while calcium hydroxide-based paste stimulated the lowest expression of these gene markers. For M2 protein markers, BioRootTM RCS presented the highest stimulation while calcium hydroxide-based paste also presented the lowest stimulation. It was concluded that all the evaluated filling materials increased the genetic expression of pro- and anti-inflammatory markers: TNF-α and IL-10 respectively. The others proinflammatory mediators showed differences against the filling materials. However, this process did not induce the inflammatory response polarization, resulting in a hybrid macrophage.
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Affiliation(s)
- Raquel Assed Bezerra Da Silva
- Departamento de Clínica Infantil- Universidade de São Paulo, Faculdade de Odontologia de Ribeirão Preto, Ribeirão Preto, São Paulo, Brasil
| | - Léa Assed Bezerra Da Silva
- Departamento de Clínica Infantil- Universidade de São Paulo, Faculdade de Odontologia de Ribeirão Preto, Ribeirão Preto, São Paulo, Brasil
| | - Edson Alves Gabriel-Junior
- Departamento de Análises Clínicas, Toxicológicas e Bromatológicas- Universidade de São Paulo, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Ribeirão Preto, São Paulo, Brasil
| | - Carlos Arterio Sorgi
- Departamento de Química - Universidade de São Paulo, Faculdade de Filosofia Ciência e Letras de Ribeirão Preto, Ribeirão Preto, São Paulo, Brasil
| | - Lúcia Helena Faccioli
- Departamento de Análises Clínicas, Toxicológicas e Bromatológicas- Universidade de São Paulo, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Ribeirão Preto, São Paulo, Brasil
| | - Vivian Vicentin Massoni
- Departamento de Clínica Infantil- Universidade de São Paulo, Faculdade de Odontologia de Ribeirão Preto, Ribeirão Preto, São Paulo, Brasil
| | - Paulo Nelson-Filho
- Departamento de Clínica Infantil- Universidade de São Paulo, Faculdade de Odontologia de Ribeirão Preto, Ribeirão Preto, São Paulo, Brasil
| | - Carolina Maschietto Pucinelli
- Departamento de Clínica Infantil- Universidade de São Paulo, Faculdade de Odontologia de Ribeirão Preto, Ribeirão Preto, São Paulo, Brasil
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Dal-Fabbro R, Cosme-Silva L, Capalbo LC, Chaves-Neto AH, Ervolino E, Cintra LTA, Gomes-Filho JE. Excessive caffeine intake increases bone resorption associated with periapical periodontitis in rats. Int Endod J 2021; 54:1861-1870. [PMID: 34037986 DOI: 10.1111/iej.13578] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 05/19/2021] [Accepted: 05/21/2021] [Indexed: 12/31/2022]
Abstract
AIM To evaluate the effect of excessive caffeine intake on the inflammation/resorption processes associated with periapical periodontitis (PP) in rats. METHODOLOGY Sixteen Wistar rats were used. Periapical periodontitis was induced in the four first molars in each animal. The animals were arranged into two groups: control (C)-rats with periapical periodontitis; and caffeine (CAF)-rats with periapical periodontitis under caffeine administration protocol. The CAF animals received 10 mg/100 g of body weight/day of caffeine via gavage starting fifteen days before PP induction and continuing for thirty more days until euthanasia. On the 30th day, the animals were euthanized and the jaws removed for microcomputed tomography, histological and immunohistochemical analysis for RANKL, OPG, TRAP, IL-10, TNF-⍺ and IL-1β. The Mann-Whitney test was performed for nonparametric data, and Student's t test was performed for parametric data, using p < .05. RESULTS There was no significant difference in the weight change between the groups. The median score of the inflammatory process was significantly greater in the CAF group (3) compared with the C group (2), p = .0256. Bone resorption was greater in the group consuming caffeine (1.08 ± 0.15 mm3 ) compared with the C group (0.88 ± 0.10 mm3 ), p = .0346. The immunolabelling for RANKL, TRAP and IL-1β was significantly higher in the CAF group when compared to the control, p < .05. No differences were found for the OPG, IL-10 and TNF-⍺ immunolabelling. CONCLUSION Excessive caffeine exposure via gavage in rats was able to exacerbate the volume of periapical bone destruction, and the inflammatory pattern deriving from periapical periodontitis altering the expression of RANKL, IL-1β and TRAP.
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Affiliation(s)
- Renan Dal-Fabbro
- Department of Preventive and Restorative Dentistry, Araçatuba, Brazil
| | - Leopoldo Cosme-Silva
- Department of Restorative Dentistry and Endodontics, School of Dentistry, Federal University of Alagoas (UFAL), Alagoas, Brazil
| | | | | | - Edilson Ervolino
- Department of Basic Science, School of Dentistry, São Paulo State University (Unesp), Araçatuba, Brazil
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Production of TNF-𝛼 by macrophages stimulated with endodontic pathogens and its effect on the biological properties of stem cells of the apical papilla. Clin Oral Investig 2021; 25:5307-5315. [PMID: 33624201 DOI: 10.1007/s00784-021-03839-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 02/15/2021] [Indexed: 01/09/2023]
Abstract
OBJECTIVES The first objective of the present study was to investigate TNF-𝛼 secretion by macrophages stimulated with endodontic pathogens and bacterial cell surface components. The second objective was to assess the in vitro effects of TNF-𝛼 on periostin, cytokine, and matrix metalloproteinase (MMP) secretion by and the viability, proliferation rate, and mineralization potential of stem cells of the apical papilla (SCAP). METHODS TNF-𝛼 secretion by macrophages stimulated with either endodontic pathogens or bacterial surface components was assessed using an enzyme-linked immunosorbent assay (ELISA). The viability and proliferation rate of SCAP treated with TNF-𝛼 were assessed using a colorimetric MTT assay. The mineralization potential of TNF-𝛼-treated SCAP was determined by Alizarin Red staining. Periostin secretion by SCAP was determined by ELISA while cytokine and MMP secretion were assessed using a multiplexing laser bead assay. RESULTS TNF-𝛼 secretion by macrophages increased following a stimulation with Gram-negative and Gram-positive endodontic pathogens. Lipopolysaccharide and lipoteichoic acid also dose-dependently increased the secretion of TNF-𝛼 by macrophages. The viability, proliferation rate, and mineralization activity of SCAP were negatively affected by a TNF-𝛼 treatment. Treating SCAP with TNF-𝛼 attenuated the secretion of periostin and upregulated the secretion of several cytokines and MMPs. CONCLUSIONS TNF-𝛼 exerts deleterious effects on SCAP by affecting their viability, proliferation rate, and mineralization potential. By its ability to induce the secretion of pro-inflammatory cytokines and MMPs by SCAP, TNF-𝛼 can contribute to creating an inflammatory environment, promoting tissue destruction, and consequently interfering with the success of regenerative endodontic therapy. CLINICAL RELEVANCE TNF-𝛼 has deleterious impacts on stem cells of the apical papilla and may compromise the outcome of regenerative endodontic therapy.
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Park OJ, Kwon Y, Park C, So YJ, Park TH, Jeong S, Im J, Yun CH, Han SH. Streptococcus gordonii: Pathogenesis and Host Response to Its Cell Wall Components. Microorganisms 2020; 8:microorganisms8121852. [PMID: 33255499 PMCID: PMC7761167 DOI: 10.3390/microorganisms8121852] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 11/23/2020] [Accepted: 11/23/2020] [Indexed: 02/08/2023] Open
Abstract
Streptococcus gordonii, a Gram-positive bacterium, is a commensal bacterium that is commonly found in the skin, oral cavity, and intestine. It is also known as an opportunistic pathogen that can cause local or systemic diseases, such as apical periodontitis and infective endocarditis. S. gordonii, an early colonizer, easily attaches to host tissues, including tooth surfaces and heart valves, forming biofilms. S. gordonii penetrates into root canals and blood streams, subsequently interacting with various host immune and non-immune cells. The cell wall components of S. gordonii, which include lipoteichoic acids, lipoproteins, serine-rich repeat adhesins, peptidoglycans, and cell wall proteins, are recognizable by individual host receptors. They are involved in virulence and immunoregulatory processes causing host inflammatory responses. Therefore, S.gordonii cell wall components act as virulence factors that often progressively develop diseases through overwhelming host responses. This review provides an overview of S. gordonii, and how its cell wall components could contribute to the pathogenesis and development of therapeutic strategies.
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Affiliation(s)
- Ok-Jin Park
- Department of Oral Microbiology and Immunology, School of Dentistry, Dental Research Institute, Seoul National University, Seoul 08826, Korea; (O.-J.P.); (Y.K.); (C.P.); (Y.J.S.); (T.H.P.); (S.J.); (J.I.)
| | - Yeongkag Kwon
- Department of Oral Microbiology and Immunology, School of Dentistry, Dental Research Institute, Seoul National University, Seoul 08826, Korea; (O.-J.P.); (Y.K.); (C.P.); (Y.J.S.); (T.H.P.); (S.J.); (J.I.)
| | - Chaeyeon Park
- Department of Oral Microbiology and Immunology, School of Dentistry, Dental Research Institute, Seoul National University, Seoul 08826, Korea; (O.-J.P.); (Y.K.); (C.P.); (Y.J.S.); (T.H.P.); (S.J.); (J.I.)
| | - Yoon Ju So
- Department of Oral Microbiology and Immunology, School of Dentistry, Dental Research Institute, Seoul National University, Seoul 08826, Korea; (O.-J.P.); (Y.K.); (C.P.); (Y.J.S.); (T.H.P.); (S.J.); (J.I.)
| | - Tae Hwan Park
- Department of Oral Microbiology and Immunology, School of Dentistry, Dental Research Institute, Seoul National University, Seoul 08826, Korea; (O.-J.P.); (Y.K.); (C.P.); (Y.J.S.); (T.H.P.); (S.J.); (J.I.)
| | - Sungho Jeong
- Department of Oral Microbiology and Immunology, School of Dentistry, Dental Research Institute, Seoul National University, Seoul 08826, Korea; (O.-J.P.); (Y.K.); (C.P.); (Y.J.S.); (T.H.P.); (S.J.); (J.I.)
| | - Jintaek Im
- Department of Oral Microbiology and Immunology, School of Dentistry, Dental Research Institute, Seoul National University, Seoul 08826, Korea; (O.-J.P.); (Y.K.); (C.P.); (Y.J.S.); (T.H.P.); (S.J.); (J.I.)
| | - Cheol-Heui Yun
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea;
- Institute of Green Bio Science Technology, Seoul National University, Pyeongchang 25354, Korea
| | - Seung Hyun Han
- Department of Oral Microbiology and Immunology, School of Dentistry, Dental Research Institute, Seoul National University, Seoul 08826, Korea; (O.-J.P.); (Y.K.); (C.P.); (Y.J.S.); (T.H.P.); (S.J.); (J.I.)
- Correspondence: ; Tel.: +82-2-880-2310
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Yin W, Dong M, Ye D, Liu Q, Liu S, Shi C, Bai H, Wang Q, Yang X, Wang L, Niu W. Cathepsin C promotes the progression of periapical periodontitis. Sci Bull (Beijing) 2020; 65:951-957. [PMID: 36747428 DOI: 10.1016/j.scib.2019.12.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 11/13/2019] [Accepted: 11/20/2019] [Indexed: 02/08/2023]
Abstract
Although the role of cathepsin C (Cat C) in inflammation is gradually being elucidated, its function in periapical periodontitis, which is one of the most common infectious diseases worldwide, has not been studied. This study evaluated a surgically-induced model of periapical periodontitis in cathepsin C (Cat C) knock-down (KD) mice, which was constructed with a tetracycline operator, to evaluate the role of Cat C in the pathogenesis and progression of periapical periodontitis. Our results showed, for the first time, that there was a statistically significant increase in the expression of Cat C as periapical periodontitis progressed; this increase started from 1 week after surgery and reached a peak at 3 weeks after surgery, before gradually decreasing. The volume of periapical bone resorption in Cat C KD mice was significantly smaller than that in wild-type mice at 3 and 4 weeks after surgery (P<0.05). Inflammatory cell infiltration into the apical tissues of wild-type mice was also significantly higher than that of Cat C KD mice. The expression of receptor activator of nuclear factor-κB ligand (RANKL) in wild-type mice was also higher than that in Cat C KD mice. The difference in the number of osteoclasts in the apical area between the two groups was statistically significant after 2 weeks. Correlation analysis showed that there was a significant correlation between Cat C and RANKL expression (r= 0.835). Therefore, our data indicated that Cat C promoted the apical inflammation and bone destruction in mice.
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Affiliation(s)
- Wei Yin
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine (Ministry of Education), School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China; Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth College, One Medical Center Drive, Lebanon, NH 03756, USA
| | - Ming Dong
- School of Stomatology, Dalian Medical University, Dalian 116044, China
| | - Dandan Ye
- Hospital of Stomatology, Yiwu City, Jinhua 322005, China
| | - Qicheng Liu
- School of Stomatology, Dalian Medical University, Dalian 116044, China
| | - Shuo Liu
- School of Stomatology, Dalian Medical University, Dalian 116044, China
| | - Chun Shi
- School of Stomatology, Dalian Medical University, Dalian 116044, China
| | - Hua Bai
- School of Stomatology, Dalian Medical University, Dalian 116044, China
| | - Qian Wang
- School of Stomatology, Dalian Medical University, Dalian 116044, China
| | - Xue Yang
- School of Stomatology, Dalian Medical University, Dalian 116044, China
| | - Lina Wang
- School of Stomatology, Dalian Medical University, Dalian 116044, China.
| | - Weidong Niu
- School of Stomatology, Dalian Medical University, Dalian 116044, China.
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Martinho FC, de Rabello DGD, Ferreira LL, Nascimento GG. Participation of endotoxin in root canal infections: A systematic review and meta-analysis. Eur J Dent 2019; 11:398-406. [PMID: 28932155 PMCID: PMC5594974 DOI: 10.4103/ejd.ejd_84_17] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
This systematic review and meta-analysis aimed to evaluate the relationship between endotoxin levels and presence of clinical signs/symptoms and radiographic features in patients with endodontic infection. Electronic searches were performed on Medline/PubMed, Embase, Cochrane Library, Scielo, Science Direct, Web of Knowledge and Scopus databases for identification of relevant studies published up to December 2016. Grey literature was searched in Google Scholar. The selected literature was reviewed independently by two authors. Clinical studies evaluating the levels of endotoxin and the presence of clinical and radiographic features were included in this review. In order to determine the relationship between endotoxin levels and presence of clinical signs/symptoms and radiographic features meta-analyses were performed. Among the 385 articles identified in the initial search, 30 were included for full-text appraisal and only eight studies met the inclusion criteria for this systematic review. Meta-analysis revealed that individuals having teeth with tenderness to percussion (TTP) (P = 0.04; I2 57%) and previous episode of pain (PEP) (P = 0.001; I2 81%) had higher levels of endotoxin than their counterparts. Size of radiographic lesion >2 mm (P = 0.02; I2 68%) and presence of root canal exudation (EX) (P = 0.0007; I2 0%) were associated with higher levels of endotoxin. This systematic review and meta-analyses provided a strong evidence that endotoxin are related with the presence of clinical signs/symptoms and radiographic features in patients with endodontic infection.
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Affiliation(s)
- Frederico Canato Martinho
- Department of Restorative Dentistry, São José dos Campos Dental School, State University of São Paulo, São Paulo
| | | | - Luciana Louzada Ferreira
- Department of Restorative Dentistry, São José dos Campos Dental School, State University of São Paulo, São Paulo
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Ceccarelli F, Saccucci M, Di Carlo G, Lucchetti R, Pilloni A, Pranno N, Luzzi V, Valesini G, Polimeni A. Periodontitis and Rheumatoid Arthritis: The Same Inflammatory Mediators? Mediators Inflamm 2019; 2019:6034546. [PMID: 31191116 PMCID: PMC6525860 DOI: 10.1155/2019/6034546] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 02/06/2019] [Indexed: 02/07/2023] Open
Abstract
The strict link between periodontitis (PD) and rheumatoid arthritis (RA) has been widely demonstrated by several studies. PD is significantly more frequent in RA patients in comparison with healthy subjects: this prevalence is higher in individuals at the earliest stages of disease and in seropositive patients. This is probably related to the role of P. gingivalis in inducing citrullination and leading to the development of the new antigens. Despite the many studies conducted on this topic, there is very little data available concerning the possibility to use the same biomarkers to evaluate both RA and PD patients. The aim of the review is to summarize this issue. Starting from genetic factors, data from literature demonstrated the association between HLA-DRB1 alleles and PD susceptibility, similar to RA patients; moreover, SE-positive patients showed simultaneously structural damage to the wrist and periodontal sites. Contrasting results are available concerning other genetic polymorphisms. Moreover, the possible role of proinflammatory cytokines, such as TNF and IL6 and autoantibodies, specifically anticyclic citrullinated peptide antibodies, has been examined, suggesting the need to perform further studies to better define this issue.
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Affiliation(s)
- Fulvia Ceccarelli
- Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Matteo Saccucci
- Department of Oral and Maxillo-Facial Sciences, Sapienza University of Rome, Viale Regina Elena 287a, 00161 Rome, Italy
| | - Gabriele Di Carlo
- Department of Oral and Maxillo-Facial Sciences, Sapienza University of Rome, Viale Regina Elena 287a, 00161 Rome, Italy
| | - Ramona Lucchetti
- Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Andrea Pilloni
- Department of Oral and Maxillo-Facial Sciences, Sapienza University of Rome, Viale Regina Elena 287a, 00161 Rome, Italy
| | - Nicola Pranno
- Department of Oral and Maxillo-Facial Sciences, Sapienza University of Rome, Viale Regina Elena 287a, 00161 Rome, Italy
| | - Valeria Luzzi
- Department of Oral and Maxillo-Facial Sciences, Sapienza University of Rome, Viale Regina Elena 287a, 00161 Rome, Italy
| | - Guido Valesini
- Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Antonella Polimeni
- Department of Oral and Maxillo-Facial Sciences, Sapienza University of Rome, Viale Regina Elena 287a, 00161 Rome, Italy
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Virdee SS, Butt K, Grant M, Camilleri J, Cooper PR, Tomson PL. A systematic review of methods used to sample and analyse periradicular tissue fluid during root canal treatment. Int Endod J 2019; 52:1108-1127. [DOI: 10.1111/iej.13104] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Accepted: 02/22/2019] [Indexed: 01/01/2023]
Affiliation(s)
- S. S. Virdee
- Department of Restorative Dentistry Institute of Clinical Sciences The University of Birmingham School of Dentistry Birmingham UK
| | - K. Butt
- Department of Restorative Dentistry Institute of Clinical Sciences The University of Birmingham School of Dentistry Birmingham UK
| | - M. Grant
- Department of Restorative Dentistry Institute of Clinical Sciences The University of Birmingham School of Dentistry Birmingham UK
| | - J. Camilleri
- Department of Restorative Dentistry Institute of Clinical Sciences The University of Birmingham School of Dentistry Birmingham UK
| | - P. R. Cooper
- Department of Restorative Dentistry Institute of Clinical Sciences The University of Birmingham School of Dentistry Birmingham UK
| | - P. L. Tomson
- Department of Restorative Dentistry Institute of Clinical Sciences The University of Birmingham School of Dentistry Birmingham UK
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Chow AT, Quah SY, Bergenholtz G, Lim KC, Yu VSH, Tan KS. Bacterial species associated with persistent apical periodontitis exert differential effects on osteogenic differentiation. Int Endod J 2018; 52:201-210. [PMID: 30099741 DOI: 10.1111/iej.12994] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Accepted: 08/06/2018] [Indexed: 01/11/2023]
Abstract
AIM To determine if bacteria associated with persistent apical periodontitis induce species-specific pro-inflammatory cytokine responses in macrophages, and the effects of this species-specific microenvironment on osteogenic differentiation. METHODOLOGY Macrophages were exposed to Enterococcus faecalis, Streptococcus oralis, Streptococcus mitis, Fusobacterium nucleatum, Treponema denticola or Tannerella forsythia, and levels of TNF-α and IL-1β elicited were determined by immunoassay. Following treatment of MG-63 pre-osteoblasts with conditioned media from bacteria-exposed macrophages, osteogenic differentiation and viability of osteoblasts were analyzed by Alizarin Red Staining and MTS assay, respectively. Statistical analysis was carried out by one-way anova with the Tukey post-hoc test. Differences were considered to be significant if P < 0.05. RESULTS Macrophages exposed to Gram-positive bacteria did not produce significant amounts of cytokines. F. nucleatum-challenged macrophages produced up to four-fold more TNF-α and IL-1β compared to T. denticola or T. forsythia. Only conditioned media from macrophages treated with Gram-negative bacteria decreased mineralization and viability of osteoblasts. CONCLUSIONS Gram-positive bacteria did not impact osteogenic differentiation and appeared innocuous. Gram-negative bacteria, in particular F. nucleatum elicited an enhanced pro-inflammatory response in macrophages, inhibited osteogenic differentiation and reduced cell viability. The findings suggest that the presence of this organism could potentially increase the severity of persistent apical periodontitis.
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Affiliation(s)
- A T Chow
- Faculty of Dentistry, National University of Singapore, Singapore, Singapore
| | - S Y Quah
- Faculty of Dentistry, National University of Singapore, Singapore, Singapore
| | - G Bergenholtz
- The Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - K C Lim
- Faculty of Dentistry, National University of Singapore, Singapore, Singapore
| | - V S H Yu
- Faculty of Dentistry, National University of Singapore, Singapore, Singapore
| | - K S Tan
- Faculty of Dentistry, National University of Singapore, Singapore, Singapore
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Dessaune Neto N, Porpino MTM, Antunes HDS, Rodrigues RCV, Perez AR, Pires FR, Siqueira JF, Armada L. Pro-inflammatory and anti-inflammatory cytokine expression in post-treatment apical periodontitis. J Appl Oral Sci 2018; 26:e20170455. [PMID: 29898177 PMCID: PMC5963913 DOI: 10.1590/1678-7757-2017-0455] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Accepted: 01/18/2018] [Indexed: 11/21/2022] Open
Abstract
OBJECTIVE This study evaluated the expression of pro-inflammatory (IL-1β, IL-6, IFN-γ and TNF-α) and anti-inflammatory (IL-4 and TGF-β) cytokines in apical periodontitis lesions. Correlations between these cytokines and clinical and cone-beam computed tomographic (CBCT) data were also assessed. MATERIAL AND METHODS Apical periodontitis lesions' data were obtained from 27 patients subjected to periradicular surgery. Specimens were processed for histopathologic and immunohistochemical analysis. Sections were evaluated according to the amount of positive staining for each antibody. Expression levels of the target mediators were compared with clinical and CBCT data. RESULTS Twenty lesions were diagnosed as granuloma and 7 as cyst. In granulomas, IL-4 expression was significantly higher than IL-6 (p=0.001) and TNF-α (p=0.001). There was a significant relationship between high levels of TNF-α and lesions <5 mm (p=0.017). In cysts, IL-6 expression was significant lower than IL-4 (p=0.001) and IFN-γ (p=0.004). There was a significant relationship between high levels of TGF-β and endodontic treatment performed ≤4 years before (p=0.045). In general, IL-4 was the most expressed mediator in both cysts and granulomas. CONCLUSIONS There was a balance between the expression of pro-inflammatory and anti-inflammatory cytokines associated with the chronic periradicular inflammatory process. TNF-α and TGF-β were related to some clinical and CBCT data.
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Affiliation(s)
- Nilton Dessaune Neto
- Universidade Estácio de Sá, Faculdade de Odontologia, Departamento de Endodontia, Rio de Janeiro, RJ, Brasil
| | | | - Henrique Dos Santos Antunes
- Universidade Estácio de Sá, Faculdade de Odontologia, Departamento de Endodontia, Rio de Janeiro, RJ, Brasil
| | - Renata Costa Val Rodrigues
- Universidade Estácio de Sá, Faculdade de Odontologia, Departamento de Endodontia, Rio de Janeiro, RJ, Brasil.,Universidade Veiga de Almeida, Faculdade de Odontologia, Departamento de Endodontia, Rio de Janeiro, RJ, Brasil
| | - Alejandro Ron Perez
- Universidade Estácio de Sá, Faculdade de Odontologia, Departamento de Endodontia, Rio de Janeiro, RJ, Brasil
| | - Fábio Ramôa Pires
- Universidade Estácio de Sá, Faculdade de Odontologia, Departamento de Endodontia, Rio de Janeiro, RJ, Brasil
| | - José Freitas Siqueira
- Universidade Estácio de Sá, Faculdade de Odontologia, Departamento de Endodontia, Rio de Janeiro, RJ, Brasil
| | - Luciana Armada
- Universidade Estácio de Sá, Faculdade de Odontologia, Departamento de Endodontia, Rio de Janeiro, RJ, Brasil
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Salles AG, Antunes LAA, Küchler EC, Antunes LS. Association between Apical Periodontitis and Interleukin Gene Polymorphisms: A Systematic Review and Meta-analysis. J Endod 2018; 44:355-362. [PMID: 29306532 DOI: 10.1016/j.joen.2017.11.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Revised: 09/08/2017] [Accepted: 11/06/2017] [Indexed: 10/18/2022]
Abstract
INTRODUCTION Genetic polymorphisms may result in altered gene expression or functional changes of the encoded molecules and could possibly generate a deficient immunity. Consequently, individuals with specific genotypes could be more susceptible to disease or could present an increase in disease severity. Our study is aimed to verify, through a systematic review and meta-analysis registered in the PROSPERO database (CRD42016043905), whether currently available evidence supports a relationship between interleukin gene polymorphisms and apical periodontitis (AP). METHODS A broad search for studies was conducted. The following databases were used: PubMed, Scopus, Web of Science, and the Virtual Health Library (MEDLINE, SciELO, IBECS, and LILACS). The Medical Subject Headings (MeSH) terms "Periapical Periodontitis," "Periapical Abscess," "Polymorphism, Genetic," and "Polymorphism, Single Nucleotide" were used. MeSH synonyms, related terms, and free terms were included. After application of the eligibility criteria, selected studies were qualified by assessment of their methodologic quality. A fixed effects model was used for the meta-analysis. RESULTS The initial search identified 71 references. After excluding duplicate abstracts, 33 were selected. From these, 6 were eligible for quality assessment; 5 were classified as being of moderate quality, and 1 was classified as being of high quality. CONCLUSIONS From these included studies, polymorphisms in IL1B, IL6, and IL8 were associated with AP. Polymorphisms in IL1A, IL10, or IL12B were not associated with AP regardless of the methodology used. The meta-analysis suggested that the genotype and allele distribution of IL1B (+3954 C/T) gene polymorphism was different in post-treatment AP. More research in this area is warranted to confirm these results.
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Affiliation(s)
- Alessandro G Salles
- Postgraduate Program, School of Dentistry, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil
| | - Lívia A A Antunes
- Department of Specific Formation, School of Dentistry, Fluminense Federal University, Nova Friburgo, Rio de Janeiro, Brazil
| | - Erika Calvano Küchler
- Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Leonardo S Antunes
- Department of Specific Formation, School of Dentistry, Fluminense Federal University, Nova Friburgo, Rio de Janeiro, Brazil.
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Salles AG, Antunes LAA, Carvalho PA, Küchler EC, Antunes LS. Association Between Apical Periodontitis and TNF-α -308 G>A Gene Polymorphism: A Systematic Review and Meta-Analysis. Braz Dent J 2017; 28:535-542. [DOI: 10.1590/0103-6440201701491] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Accepted: 04/29/2017] [Indexed: 01/17/2023] Open
Abstract
Abstract Currently, investigations have focused on the identification of Single Nucleotide Polymorphisms (SNP) involved in host response and its ability to generate an immunity deficiency. The aim of this study was to perform a systematic review (SR) and meta-analysis to evaluate the association between TNF-α -308 G>A polymorphism and apical periodontitis (AP) phenotypes. A broad search for studies was conducted. The following databases were used: PubMed, Scopus, Web of Science, and VHL (Medline, SciELO, Ibecs, and Lilacs). The MeSH terms “Periapical Periodontitis,” “Periapical Abscess,” “Polymorphism, Genetic,” and “Polymorphism, Single Nucleotide” were used. MeSH synonyms, related terms, and free terms were included. Clinical investigations of individuals with different AP phenotypes in permanent teeth were selected. After application of the eligibility criteria, selected studies were qualified by assessing their methodological quality. A fixed effect model was used for the meta-analysis. The initial search identified 71 references. After excluding duplicate abstracts, 33 were selected. From these, two were eligible for quality assessment and were classified as being of moderate evidence. The included studies did not demonstrate association between AP and TNF-α -308 G>A SNP. However, the meta-analysis demonstrated an association between the genotype distribution and AP phenotype (OR= 0.49; confidence interval= 0.25, 0.96; p=0.04). The role of TNF-α -308 G>A SNP in AP phenotypes is debatable. Further studies are needed to confirm and understand the underlying mechanisms of the identified association.
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Rodrigues JT, Dos Santos Antunes H, Armada L, Pires FR. Influence of surgical decompression on the expression of inflammatory and tissue repair biomarkers in periapical cysts. Oral Surg Oral Med Oral Pathol Oral Radiol 2017; 124:561-567. [PMID: 28822696 DOI: 10.1016/j.oooo.2017.06.121] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Revised: 06/21/2017] [Accepted: 06/22/2017] [Indexed: 12/15/2022]
Abstract
OBJECTIVE The biologic effects of surgical decompression on the epithelium and connective tissues of periapical cysts are not fully understood. The aim of this study was to evaluate the expression of tissue repair and inflammatory biomarkers in periapical cysts before and after surgical decompression. STUDY DESIGN Nine specimens of periapical cysts treated with decompression before undergoing complete enucleation were immunohistochemically analyzed to investigate the expression of interleukin-1β, tumor necrosis factor-α, transforming growth factor-β1, matrix metalloproteinase-9, Ki-67, and epidermal growth factor receptor. Expression of the biomarkers was classified as positive, focal, or negative. Ki-67 immunoexpression was calculated as a cell proliferation index. The expression of the biomarkers was compared in the specimens from decompression and from the final surgical procedure. RESULTS Computed tomography demonstrated that volume was reduced in all cysts after decompression. There were no differences in the immunoexpression of the proinflammatory and tissue repair biomarkers when comparing the specimens obtained before and after the decompression. CONCLUSIONS Surgical decompression was efficient in reducing the volume of periapical cysts before complete enucleation. When comparing the specimens obtained from surgical decompression and from complete surgical removal, the immunohistochemical analysis did not show a decrease in proinflammatory biomarkers; neither did it show an increase in tissue repair biomarkers.
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Affiliation(s)
| | | | - Luciana Armada
- Post-graduation Program in Dentistry, Estácio de Sá University, Rio de Janeiro, Brazil
| | - Fábio Ramôa Pires
- Post-graduation Program in Dentistry, Estácio de Sá University, Rio de Janeiro, Brazil.
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Effect of iRoot SP and mineral trioxide aggregate (MTA) on the viability and polarization of macrophages. Arch Oral Biol 2017; 80:27-33. [PMID: 28364673 DOI: 10.1016/j.archoralbio.2017.03.010] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Revised: 12/19/2016] [Accepted: 03/12/2017] [Indexed: 12/22/2022]
Abstract
OBJECTIVE This study was performed to investigate the effect of iRoot SP and mineral trioxide aggregate (MTA) on the viability and polarization of macrophages. METHODS The effect of iRoot SP and MTA on the viability of RAW 264.7 macrophages was tested using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay after 1 and 2days of culture. The gene expression levels of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), interleukin 10 (IL-10), interleukin 12p40 (IL-12p40) were measured by quantitative real time polymerase chain reaction (qRT-PCR) after stimulation of the RAW 264.7 macrophages with iRoot SP and MTA. The expression levels of CD11c and CD206 in RAW 264.7 macrophages were examined by immunofluorescence and flow cytometry after stimulation with iRoot SP and MTA. The data were analyzed by one-way analysis of variance and the Tukey test. RESULTS Both iRoot SP and MTA were non-toxic to the RAW 264.7 macrophages. The use of iRoot SP and MTA increased the expression of IL-1β, TNF-α, IL-10, IL-12p40 on the first day of culture and could promote macrophage M1 and M2 polarization. CONCLUSIONS MTA and iRoot SP have good biocompatibility with macrophages, and they induced both M1 and M2 polarization of the RAW 264.7 macrophages.
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p-Hydroxyacetophenone suppresses nuclear factor-κB-related inflammation in nociceptive and inflammatory animal models. J Nat Med 2017; 71:422-432. [DOI: 10.1007/s11418-017-1074-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2016] [Accepted: 01/17/2017] [Indexed: 01/24/2023]
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Effects of Abutment Removal and Reconnection on Inflammatory Cytokine Production Around Dental Implants. IMPLANT DENT 2015; 24:730-4. [DOI: 10.1097/id.0000000000000330] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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Lu B, Zhang J, Huang X, Xiao S, Zhang M, Cai Z. Expression of Interleukin-1β and Matrix Metalloproteinase-8 in Cytolytic and Noncytolytic Enterococcus faecalis–induced Persistent Apical Periodontitis: A Comparative Study in the Rat. J Endod 2015; 41:1288-93. [DOI: 10.1016/j.joen.2015.04.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2014] [Revised: 03/18/2015] [Accepted: 04/28/2015] [Indexed: 01/12/2023]
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A small molecule, odanacatib, inhibits inflammation and bone loss caused by endodontic disease. Infect Immun 2015; 83:1235-45. [PMID: 25583522 DOI: 10.1128/iai.01713-14] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Periapical disease, an inflammatory disease mainly caused by dental caries, is one of the most prevalent infectious diseases of humans, affecting both children and adults. The infection travels through the root, leading to inflammation, bone destruction, and severe pain for the patient. Therefore, the development of a new class of anti-periapical disease therapies is necessary and critical for treatment and prevention. A small molecule, odanacatib (ODN), which is a cathepsin K (Ctsk) inhibitor, was investigated to determine its ability to treat this disease in a mouse model of periapical disease. While Ctsk was originally found in osteoclasts as an osteoclast-specific lysosomal protease, we were surprised to find that ODN can suppress the bacterium-induced immune response as well as bone destruction in the lesion area. X rays and microcomputed tomography (micro-CT) showed that ODN treatment had significant bone protection effects at different time points. Immunohistochemical and immunofluorescent staining show that ODN treatment dramatically decreased F4/80+ macrophages and CD3+ T cells in the lesion areas 42 days after infection. Consistent with these findings, quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) analysis showed low levels of proinflammatory mRNAs (for tumor necrosis factor alpha, interleukin 6, and interleukin 23α) and corresponding cytokine expression in the ODN-treated disease group. The levels of mRNA for Toll-like receptors 4, 5, and 9 also largely decreased in the ODN-treated disease group. Our results demonstrated that ODN can inhibit endodontic disease development, bone erosion, and immune response. These results indicate that application of this small molecule offers a new opportunity to design effective therapies that could prevent periapical inflammation and revolutionize current treatment options.
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Liao JC, Chang WT, Lee MS, Chiu YJ, Chao WK, Lin YC, Lin MK, Peng WH. Antinociceptive and anti-inflammatory activities of Cuscuta chinensis seeds in mice. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2014; 42:223-42. [PMID: 24467546 DOI: 10.1142/s0192415x14500153] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
The seeds of Cuscuta chinensis, Cuscutae Semen, are commonly used as a medicinal material for treating the aching and weakness of the loins and knees, tonifying the defects of the liver and the kidney, and treating the diarrhea due to hypofunction of the kidney and the spleen. Since aching and inflammation are highly correlated with such diseases, the aim of this study is to investigate the possible antinociceptive and anti-inflammatory mechanisms of the seeds of C. chinensis. The antinociceptive effect of the seeds of C. chinensis was evaluated via the acetic acid-induced writhing response and formalin-induced paw licking methods. The anti-inflammatory effect was evaluated via the λ-carrageenan induced mouse paw edema method. The results found that 100 and 500 mg/kg of the methanol extract of the seeds of C. chinensis( CC MeOH ) significantly decreased (p < 0.01 and p < 0.001, respectively) the writhing response in the acetic acid assay. Additionally, 20-500 mg/kg of CC MeOH significantly decreased licking time at the early (20 and 100 mg/kg, p < 0.001) and late phases (100 mg/kg, p < 0.01; 500 mg/kg, p < 0.001) of the formalin test, respectively. Furthermore, CC MeOH (100 and 500 mg/kg) significantly decreased (p < 0.01 and p < 0.001, respectively) edema paw volume four hours after λ-carrageenan had been injected. The results in the following study also revealed that the anti-inflammatory mechanism of CC MeOH may be due to declined levels of NO and MDA in the edema paw by increasing the activities of SOD, GPx and GRd in the liver. In addition, CC MeOH also decreased IL-1β, IL-6, NF-κB, TNF-α, and COX-2 levels. This is the first study to demonstrate the possible mechanisms for the antinociceptive and anti-inflammatory effects of CC MeOH in vivo. Thus, it provides evidence for the treatment of Cuscutae Semen in inflammatory diseases.
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Affiliation(s)
- Jung-Chun Liao
- School of Pharmacy, College of Pharmacy, China Medical University, Taichung 404, Taiwan , Department of Pharmacy, China Medical University Hospital, Taichung 404, Taiwan
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Jakovljevic A, Knezevic A, Karalic D, Soldatovic I, Popovic B, Milasin J, Andric M. Pro-inflammatory cytokine levels in human apical periodontitis: Correlation with clinical and histological findings. AUST ENDOD J 2014; 41:72-7. [DOI: 10.1111/aej.12072] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Affiliation(s)
- Aleksandar Jakovljevic
- Clinic of Oral Surgery and Implantology; School of Dental Medicine; University of Belgrade; Belgrade Serbia
| | - Aleksandra Knezevic
- Department of Virology; Institute of Microbiology and Immunology; Faculty of Medicine; University of Belgrade; Belgrade Serbia
| | - Danijela Karalic
- Department of Virology; Institute of Microbiology and Immunology; Faculty of Medicine; University of Belgrade; Belgrade Serbia
| | - Ivan Soldatovic
- Institute of Medical Statistics and Informatics; Faculty of Medicine; University of Belgrade; Belgrade Serbia
| | - Branka Popovic
- Institute of Biology and Human Genetics; School of Dental Medicine; University of Belgrade; Belgrade Serbia
| | - Jelena Milasin
- Institute of Biology and Human Genetics; School of Dental Medicine; University of Belgrade; Belgrade Serbia
| | - Miroslav Andric
- Clinic of Oral Surgery and Implantology; School of Dental Medicine; University of Belgrade; Belgrade Serbia
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Garrido M, Dezerega A, Castro-Martínez A, Hernández M. Host-derived biomarkers in gingival crevicular fluid for complementary diagnosis of apical periodontitis. World J Stomatol 2014; 3:19-24. [DOI: 10.5321/wjs.v3.i2.19] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Revised: 05/07/2014] [Accepted: 05/14/2014] [Indexed: 02/07/2023] Open
Abstract
Apical periodontitis (AP) develops as a result of the host’s immune inflammatory response to pulpal infection of the dental root canals that leads to the generation of an apical lesion of endodontic origin (ALEO) and potentially to systemic metabolic alterations. Misdiagnosed ALEO is not infrequent due to the lack of diagnostic tools to differentiate apical lesions of different natures. Despite the conservative endodontic treatment shows a high success rate, there are refractory cases that can not be identified early enough during follow up. This evidences the need to develop complementary diagnostic tools, such as oral fluid biomarker analysis. Gingival crevicular fluid (GCF) is a serum transudate that becomes an exudate under inflammatory conditions, carrying molecules from local periodontal tissues and general circulation than can be harvested non-invasively. We aimed to review the available literature analyzing GCF composition in AP patients to evaluate whether GCF has any potential for complementary diagnosis. To the date, only few studies addressing changes of GCF components in AP are available. Most studies support GCF modifications in specific components in AP-affected teeth, suggesting that it might reflect periapical inflammation. GCF has potential for diagnostic tool, treatment follow-up and eventually to assess systemic comprise.
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Sun Z, Wang L, Peng B. Kinetics of glycogen synthase kinase (GSK)3β and phosphorylated GSK3β (Ser 9) expression in experimentally induced periapical lesions. Int Endod J 2014; 47:1107-16. [PMID: 24494585 DOI: 10.1111/iej.12258] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Accepted: 01/29/2014] [Indexed: 02/05/2023]
Abstract
AIM To investigate the kinetics of GSK3β and p-GSK3β (Ser 9) expression in experimentally induced rat periapical lesions and to explore their possible functions in the pathogenesis of periapical lesions. METHODOLOGY Periapical lesions were established in Wistar rats by occlusal pulp exposure in mandibular first molar teeth. The animals were killed on days 0, 7, 14, 21 and 28. Micro-computed tomographic, histological and enzyme histochemical analyses were performed to detect the progression of periapical lesions. Immunohistochemistry, double-dye immunofluorescence and Western blot were performed to determine the expression of GSK3β and p-GSK3β (Ser 9) in periapical tissues. RESULTS From day 0 to day 28, the lesion volume and area gradually expanded, and the GSK3β-positive cells gradually ascended. A few p-GSK3β (Ser 9)-positive cells and osteoclasts appeared on day 7 and then climaxed on day 14. The numbers then simultaneously decreased from day 21 to day 28. Western blot analysis revealed that p-GSK3β (Ser 9) and GSK3β proteins were expressed at all time-points. The positive cells and protein expression ratio of p-GSK3β (Ser 9) against GSK3β increased from day 0 to day 14 and then decreased from day 14 to day 28. Finally, double-dye immunofluorescence assay revealed that p-GSK3β (Ser 9)-positive and RANKL-positive cells were co-localized around periapical lesions on days 14 and 28. CONCLUSIONS GSK3β and p-GSK3β (Ser 9) can be observed and may be involved in alveolar bone resorption and inflammatory response in periapical lesions, as well as associated with periapical lesion pathogenesis.
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Affiliation(s)
- Z Sun
- School and Hospital of Stomatology, Wuhan University, Wuhan, China
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Liu L, Peng B. The Expression of Macrophage Migration Inhibitory Factor Is Correlated with Receptor Activator of Nuclear Factor Kappa B Ligand in Induced Rat Periapical Lesions. J Endod 2013; 39:984-9. [DOI: 10.1016/j.joen.2013.03.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2012] [Revised: 03/02/2013] [Accepted: 03/03/2013] [Indexed: 01/02/2023]
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Gao B, Zheng L. microRNA Expression in Rat Apical Periodontitis Bone Lesion. Bone Res 2013; 1:170-85. [PMID: 26273501 DOI: 10.4248/br201302006] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2013] [Accepted: 04/18/2013] [Indexed: 01/08/2023] Open
Abstract
Apical periodontitis, dominated by dense inflammatory infiltrates and increased osteoclast activities, can lead to alveolar bone destruction and tooth loss. It is believed that miRNA participates in regulating various biological processes, osteoclastogenesis included. This study aims to investigate the differential expression of miRNAs in rat apical periodontitis and explore their functional target genes. Microarray analysis was used to identify differentially expressed miRNAs in apical periodontitis. Bioinformatics technique was applied for predicting the target genes of differentially expressed miRNAs and their biological functions. The result provided us with an insight into the potential biological effects of the differentially expressed miRNAs and showed particular enrichment of target genes involved in the MAPK signaling pathways. These findings may highlight the intricate and specific roles of miRNA in inflammation and osteoclastogenesis, both of which are key aspects of apical periodontitis, thus contributing to the future investigation into the etiology, underlying mechanism and treatment of apical periodontitis.
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Affiliation(s)
- Bo Gao
- Department of Pathology, University of Alabama at Birmingham , Birmingham, USA
| | - Liwei Zheng
- Department of Orofacial Sciences, University of California , San Francisco, USA
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Tavares WLF, de Brito LCN, Henriques LCF, Oliveira RR, Maciel KF, Vieira LQ, Sobrinho APR. The impact of chlorhexidine-based endodontic treatment on periapical cytokine expression in teeth. J Endod 2013; 39:889-92. [PMID: 23791257 DOI: 10.1016/j.joen.2013.02.005] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2012] [Revised: 02/01/2013] [Accepted: 02/15/2013] [Indexed: 11/29/2022]
Abstract
INTRODUCTION Root canal treatment typically involves cleaning and shaping procedures followed by treatment with antibacterial endodontic dressing between appointments and, ultimately, 3-dimensional,hermetic filling. Chlorhexidine (CHX) is effective as an irrigation solution and is used as an endodontic dressing. The aim of this study was to examine the influence of CHX on periapical cytokine expression. METHODS Expression levels of the cytokines interferon γ, tumor necrosis factor α, interleukin (IL)-1β, IL-17A, IL-10, and the chemokine monocyte chemoattractant protein-1 (CCL2/MCP-1) were assayed by real-time polymerase chain reaction immediately after root canal cleaning and 15 days later. RESULTS Messenger RNA expression of IL-1β, interferon γ, IL-10, and CCL2/MCP-1 was increased on day 15 in teeth without endodontic dressing. No statistical change was observed in the messenger RNA expression of cytokines when comparing sampling times for teeth that received endodontic dressing. CONCLUSIONS The results show that CHX application between appointments prevented the increase of both proinflammatory and immunoregulatory cytokines 15 days after the dental procedure.
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Amaya MP, Criado L, Blanco B, Gómez M, Torres O, Flórez L, González CI, Flórez O. Polymorphisms of pro-inflammatory cytokine genes and the risk for acute suppurative or chronic nonsuppurative apical periodontitis in a Colombian population. Int Endod J 2013; 46:71-78. [PMID: 22788685 DOI: 10.1111/j.1365-2591.2012.02097.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2011] [Accepted: 06/09/2012] [Indexed: 01/04/2025]
Abstract
AIM To determine the association of functional single nucleotide polymorphisms in genes of the pro-inflammatory cytokines tumour necrosis factor-α, interleukin-1β, interleukin-8 and interleukin-12B with the development of two clinical forms of apical periodontitis (AP): acute suppurative and chronic nonsuppurative. METHODOLOGY The study included 120 patients from Bucaramanga City, Colombia, 63 diagnosed with acute suppurative AP (ASAP) and 57 diagnosed with chronic nonsuppurative AP (CNAP). Genotyping for IL1B +3954 (rs1143634), IL8 / CXCL8 -251 (rs4073), IL12B +1188 (rs3212227) and TNFA -308 (rs1800629) was performed by the PCR-restriction fragment length polymorphisms method. The statistical analysis was performed using STATA 10.0 and PLINK V1.07 software. RESULTS Significant differences in the distribution of IL8 / CXCL8 -251 A allele (P adjusted = 0.041; OR adjusted = 0.41, CI adjusted = 0.31-0.97) and IL8 / CXCL -251 TT genotype (P adjusted = 0.04; OR adjusted = 2.24, CI adjusted = 1.04-4.84) were observed comparing patients diagnosed with ASAP and CNAP. No association was observed in genotype and allele distribution for other genetic polymorphisms analysed. CONCLUSION This study provides molecular epidemiological evidence that suggests in the present cohort that IL8 / CXCL8 -251 T allele, which is associated with higher production of IL8/CXCL8, is also associated with a higher risk of developing acute suppurative form of AP, whereas IL8 / CXCL8 -251 A allele, which is associated with lower production of IL8/CXCL8, is associated with chronic nonsuppurative form of AP. This suggests a pivotal role for IL-8/CXCL8 in periapical disease because of its ability to induce chemotaxis and modulating the directed migration of neutrophils to the site of inflammation in response to microbial infection of pulp.
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Affiliation(s)
- M P Amaya
- Postgrado de Endodoncia, Facultad de Odontología, Universidad Santo Tomas, Bucaramanga, Colombia
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Zhu L, Wu Y, Wei H, Yang S, Zhan N, Xing X, Peng B. Up-regulation of IL-23 p19 expression in human periodontal ligament fibroblasts by IL-1β via concurrent activation of the NF-κB and MAPKs/AP-1 pathways. Cytokine 2012; 60:171-8. [DOI: 10.1016/j.cyto.2012.05.016] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2011] [Revised: 05/07/2012] [Accepted: 05/17/2012] [Indexed: 01/16/2023]
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Analgesic and Anti-Inflammatory Activities of Methanol Extract of Cissus repens in Mice. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2012; 2012:135379. [PMID: 22991570 PMCID: PMC3443613 DOI: 10.1155/2012/135379] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/01/2012] [Revised: 07/25/2012] [Accepted: 08/05/2012] [Indexed: 12/04/2022]
Abstract
The aim of this study was to investigate possible analgesic and anti-inflammatory mechanisms of the CRMeOH. Analgesic effect was evaluated in two models including acetic acid-induced writhing response and formalin-induced paw licking. The anti-inflammatory effect was evaluated by λ-carrageenan-induced mouse paw edema and histopathologic analyses. The results showed that CRMeOH (500 mg/kg) decreased writhing response in the acetic acid assay and licking time in the formalin test. CRMeOH (100 and 500 mg/kg) significantly decreased edema paw volume at 4th to 5th hours after λ-carrageenan had been injected. Histopathologically, CRMeOH abated the level of tissue destruction and swelling of the edema paws. These results were indicated that anti-inflammatory mechanism of CRMeOH may be due to declined levels of NO and MDA in the edema paw through increasing the activities of SOD, GPx, and GRd in the liver. Additionally, CRMeOH also decreased IL-1β, IL-6, NFκB, TNF-α, COX-2, and iNOS levels. The contents of two active ingredients, ursolic acid and lupeol, were quantitatively determined. This paper demonstrated possible mechanisms for the analgesic and anti-inflammatory effects of CRMeOH and provided evidence for the classical treatment of Cissus repens in inflammatory diseases.
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Tavares WLF, de Brito LCN, Henriques LCF, Teles FRF, Teles RP, Vieira LQ, Ribeiro Sobrinho AP. Effects of calcium hydroxide on cytokine expression in endodontic infections. J Endod 2012; 38:1368-71. [PMID: 22980179 DOI: 10.1016/j.joen.2012.06.036] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2012] [Revised: 06/29/2012] [Accepted: 06/30/2012] [Indexed: 01/02/2023]
Abstract
INTRODUCTION The use of calcium hydroxide is an effective step in killing bacteria that remain after cleaning and shaping procedures. It also induces hard-tissue formation and is effective for stopping inflammatory exudates. METHODS The aim of this study was to assay and to compare the influence of calcium hydroxide on periapical interstitial fluid from human root canals. The mRNA expression levels of the cytokines interferon (IFN)-γ, tumor necrosis factor-α, interleukin (IL)-1β, IL-17A, and IL-10 as well as the chemokine MCP-1 were assayed by real-time polymerase chain reaction immediately after root canal cleaning and 15 days later. RESULTS Levels of IL-1β, IFN-γ, IL-10, and the chemokine CCL2/MCP-1 were increased in teeth without endodontic dressings. With calcium hydroxide interappointment dressings, no statistically significant changes were observed in cytokine mRNA expression. However, when comparing teeth that received the medication with those that did not, expression levels of IL-1β, IFN-γ, and IL-10 were statistically lower in those teeth that received calcium hydroxide. CONCLUSIONS Analyses of cytokines and the chemokine CCL-2/MCP-1 demonstrated the benefits of calcium hydroxide as a root canal dressing because it impedes the increase of all mediators during the experimental time.
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Analgesic and Anti-Inflammatory Activities of Methanol Extract of Ficus pumila L. in Mice. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2012; 2012:340141. [PMID: 22666289 PMCID: PMC3359828 DOI: 10.1155/2012/340141] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/15/2011] [Revised: 02/29/2012] [Accepted: 02/29/2012] [Indexed: 12/04/2022]
Abstract
This study investigated possible analgesic and anti-inflammatory mechanisms of the methanol extract of Ficus pumila (FPMeOH). Analgesic effects were evaluated in two models including acetic acid-induced writhing response and formalin-induced paw licking. The results showed FPMeOH decreased writhing response in the acetic acid assay and licking time in the formalin test. The anti-inflammatory effect was evaluated by λ-carrageenan-induced mouse paw edema and histopathological analyses. FPMeOH significantly decreased the volume of paw edema induced by λ-carrageenan. Histopathologically, FPMeOH abated the level of tissue destruction and swelling of the edema paws. This study indicated anti-inflammatory mechanism of FPMeOH may be due to declined levels of NO and MDA in the edema paw through increasing the activities of SOD, GPx, and GRd in the liver. Additionally, FPMeOH also decreased the level of inflammatory mediators such as IL-1β, TNF-α, and COX-2. HPLC fingerprint was established and the contents of three active ingredients, rutin, luteolin, and apigenin, were quantitatively determined. This study provided evidence for the classical treatment of Ficus pumila in inflammatory diseases.
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Martinho FC, Chiesa WMM, Leite FRM, Cirelli JA, Gomes BPFA. Correlation between clinical/radiographic features and inflammatory cytokine networks produced by macrophages stimulated with endodontic content. J Endod 2012; 38:740-5. [PMID: 22595105 DOI: 10.1016/j.joen.2012.02.021] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2011] [Revised: 02/11/2012] [Accepted: 02/15/2012] [Indexed: 12/22/2022]
Abstract
INTRODUCTION Macrophages are highly activated by endodontic contents. This study investigated the correlation between different clinical signs/symptoms and radiographic features according to the levels of interleukin (IL)-1β, tumor necrosis factor α (TNF-α), IL-6, IL-10, prostaglandin E(2) (PGE(2)), and their networks produced by endodontic content-stimulated macrophages collected from primary endodontic infection with apical periodontitis (PEIAP). METHODS Samples were taken from 21 root canals with PEIAP by using paper points. The presence of exudate (EX), pain on palpation (POP), tenderness to percussion (TTP), and the size of the radiographic lesion (SRL) were recorded. Polymerase chain reaction (16S rDNA) was used for bacterial detection and limulus amebocyte lysate (LAL) assay for endotoxin measurement. Raw 264.7 macrophages were stimulated with bacterial contents during 24 hs. The amounts of IL-1β, TNF-α, IL-6, IL-10 and PGE(2) were measured by enzyme-linked immunosorbent assay. Log-based data were correlated by multiple logistic regression (P < .05). RESULTS Bacteria and endotoxin were detected in 100% of the samples. IL-6 and TNF-α were positively correlated with SRL and EX, respectively (P < .05). Clinical signs/symptoms and radiographic findings were set as dependent variables for EX-positive correlations between PGE(2), IL-1β, and TNF-α (P < .05), whereas IL-6 and PGE(2) were positively correlated to each other in POP but negatively correlated in SRL (P < .05). When POP and TTP-POP were set as dependent variables, different cytokine networks were found. CONCLUSIONS Our findings suggest different roles for each cytokine in the development of apical periodontitis, whose effects of overlapping networks depend on the signs/symptoms and radiographic features found in endodontic infection.
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Affiliation(s)
- Frederico C Martinho
- Department of Restorative Dentistry, Endodontics Division, Piracicaba Dental School, State University of Campinas, Piracicaba, São Paulo, Brazil
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Lai SC, Peng WH, Huang SC, Ho YL, Huang TH, Lai ZR, Chang YS. Analgesic and Anti-Inflammatory Activities of Methanol Extract fromDesmodium triflorumDC in Mice. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2012; 37:573-88. [DOI: 10.1142/s0192415x09007065] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
In this study, we evaluated the analgesic effect of methanol extract from Desmodium triflorum DC (MDT) by using animal models of acetic acid-induced writhing response and formalin test. The anti-inflammatory effect of MDT was investigated by λ-carrageenan-induced paw edema in mice. In order to study the anti-inflammatory mechanism of MDT, we detected the activities of glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver, the levels of interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), malondialdehyde (MDA) and nitric oxide (NO) in the edema paw tissue. In the analgesic test, MDT (0.5 and 1.0 g/kg) decreased the acetic acid-induced writhing response and the licking time on the late phase in the formalin test. In the anti-inflammatory test, MDT (0.5 and 1.0 g/kg) decreased the paw edema at the 3rd, 4th, 5th and 6th hour after λ-carrageenan administration. On the other hand, MDT increased the activities of SOD and GRd in liver tissues and decreased the MDA level in the edema paw at the 3rd hour after λ-carrageenan-induced inflammation. MDT also affected the levels of interleukin-1β, tumor necrosis factor-α, NO and MDA which were induced by λ-carrageenan. The results suggested that MDT possessed analgesic and anti-inflammatory effects. The anti-inflammatory mechanism of MDT might be related to the decreases in the level of MDA in the edema paw via increasing the activities of SOD and GRd in the liver, and the NO level via regulating the IL-1β production and the level of TNF-α in the inflamed tissues.
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Affiliation(s)
- Shang-Chih Lai
- Graduate Institute of Chinese Pharmaceutical Sciences, College of Pharmacy, China Medical University, Taichung, Taiwan
| | - Wen-Huang Peng
- Graduate Institute of Chinese Pharmaceutical Sciences, College of Pharmacy, China Medical University, Taichung, Taiwan
| | - Shun-Chieh Huang
- School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan
| | - Yu-Ling Ho
- Department of Nursing, Hung Kuang University, Taichung, Taiwan
| | - Tai-Hung Huang
- School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan
| | - Zhen-Rung Lai
- Graduate Institute of Chinese Pharmaceutical Sciences, College of Pharmacy, China Medical University, Taichung, Taiwan
| | - Yuan-Shiun Chang
- Graduate Institute of Chinese Pharmaceutical Sciences, College of Pharmacy, China Medical University, Taichung, Taiwan
- Chinese Crude Drug Pharmacy, China Medical University Hospital, Taichung, Taiwan
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Lai ZR, Peng WH, Ho YL, Huang SC, Huang TH, Lai SC, Ku YR, Tsai JC, Wang CY, Chang YS. Analgesic and Anti-Inflammatory Activities of the Methanol Extract ofKalanchoe gracilis(L.) DC Stem in Mice. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2012; 38:529-46. [DOI: 10.1142/s0192415x10008032] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
In this study, we evaluated the analgesic effect of the methanol extract of Kalanchoe gracilis (MKGS) stem in animal models by inducing writhing response with acetic acid and conducting formalin test. The anti-inflammatory effect of MKGS was also estimated on mice with λ-carrageenan induced paw edema model. In order to investigate the anti-inflammatory mechanism of MKGS, we analyzed the activities of glutathione peroxidase (GPx) and glutathione reductase (GRx) in the liver, and the levels of interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), malondialdehyde (MDA) and nitric oxide (NO) in the edema paw tissue. In the analgesic tests, MKGS (0.5 and 1.0 g/kg) decreased both the acetic acid-induced writhing response and the licking time in the late phase of the formalin test. In the anti-inflammatory test, MKGS (0.1, 0.5 and 1.0 g/kg) decreased paw edema at the third, fourth, fifth and sixth hours after λ-carrageenan had been administrated. Furthermore, MKGS increased the activities of SOD and GRx in liver tissues and decreased MDA level in the edema paws three hours after λ-carrageenan was injected. MKGS also affected the levels of IL-1β, TNF-α and NO induced by λ-carrageenan. All these results suggested that MKGS possessed analgesic and anti-inflammatory effects. The anti-inflammatory mechanism of MKGS might be related to the lowering of MDA level in the edema paw via increasing the activities of superoxide dismutase (SOD) and GRx in the liver, as well as the decreases in the levels of TNF-α and NO, and the production of IL-1β in inflamed tissues.
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Affiliation(s)
- Zhen-Rung Lai
- Graduate Institute of Chinese Pharmaceutical Sciences, College of Pharmacy, China Medical University Taichung, Taiwan
| | - Wen-Huang Peng
- Graduate Institute of Chinese Pharmaceutical Sciences, College of Pharmacy, China Medical University Taichung, Taiwan
| | - Yu-Ling Ho
- Department of Nursing, Hung Kuang University, Taichung, Taiwan
| | - Shun-Chieh Huang
- School of Pharmacy, College of Pharmacy, China Medical University Taichung, Taiwan
| | - Tai-Hung Huang
- School of Pharmacy, College of Pharmacy, China Medical University Taichung, Taiwan
| | - Shang-Chih Lai
- Graduate Institute of Chinese Pharmaceutical Sciences, College of Pharmacy, China Medical University Taichung, Taiwan
| | - Yoe-Ray Ku
- Bureau of Food and Drug Analysis, Department of Health, Executive Yuan, Taipei, Taiwan
| | - Jen-Chieh Tsai
- School of Pharmacy, College of Pharmacy, China Medical University Taichung, Taiwan
| | - Ching-Ying Wang
- Graduate Institute of Chinese Pharmaceutical Sciences, College of Pharmacy, China Medical University Taichung, Taiwan
| | - Yuan-Shiun Chang
- Graduate Institute of Chinese Pharmaceutical Sciences, College of Pharmacy, China Medical University Taichung, Taiwan
- Chinese Crude Drug Pharmacy, China Medical University Hospital, Taichung, Taiwan
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Silva MJB, Kajiya M, AlShwaimi E, Sasaki H, Hong J, Ok P, Rezende TMB, Pagonis TC, White RR, Paster BJ, Stashenko P, Kawai T. Bacteria-reactive immune response may induce RANKL-expressing T cells in the mouse periapical bone loss lesion. J Endod 2012; 38:346-50. [PMID: 22341072 DOI: 10.1016/j.joen.2011.12.029] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2011] [Revised: 12/21/2011] [Accepted: 12/22/2011] [Indexed: 10/14/2022]
Abstract
INTRODUCTION The present study investigated whether bacteria infecting the root canal can activate any infiltrating T cells to produce receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL). METHODS Using a mouse model of periapical lesion induced by artificial dental pulp exposure, the presence of RANKL-positive T cells and osteoclasts in the periapical lesion was examined by an immunohistochemical approach. The bacteria colonizing the exposed root canal were identified by 16S ribosomal RNA (rRNA) sequence analysis. The isolated endodontic bacteria were further immunized to normal mice, and soluble activator of NF-κB ligand (sRANKL) production by the T cells isolated from the immunized mice was evaluated by ex vivo culture system. RESULTS RANKL-positive T cells along with TRAP+ osteoclasts were identified in periapical bone resorption lesions. The gram-negative bacterium Pasteurella pnumotropica, which was most frequently detected from the root canal of exposed pulp, showed remarkably elevated serum immunoglobulin G (IgG)-antibody response in pulp-exposed mice compared with control nontreated mice. Immunization of mice with P. pneumotropica induced not only serum IgG-antibody but also primed bacteria-reactive T cells that produced sRANKL in response to ex vivo exposure to P. pneumotropica. CONCLUSIONS T cells infiltrating the periapical region express RANKL, and the endodontic bacteria colonizing the root canal appear to induce RANKL expression from bacteria-reactive T cells, suggesting the possible pathogenic engagement of the immune response to endodontic bacteria in the context of developing bone resorptive periapical lesions.
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Affiliation(s)
- Marcelo J B Silva
- Department of Immunology, The Forsyth Institute, Cambridge, Massachusetts, USA
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Graunaite I, Lodiene G, Maciulskiene V. Pathogenesis of apical periodontitis: a literature review. J Oral Maxillofac Res 2012; 2:e1. [PMID: 24421998 PMCID: PMC3886078 DOI: 10.5037/jomr.2011.2401] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2011] [Accepted: 09/03/2011] [Indexed: 05/29/2023]
Abstract
OBJECTIVES This review article discusses the host response in apical periodontitis with the main focus on cytokines, produced under this pathological condition and contributing to the degradation of periradicular tissues. The pace of research in this field has greatly accelerated in the last decade. Here we provide an analysis of studies published in this area during this period. MATERIAL AND METHODS Literature was selected through a search of PubMed electronic database. The keywords used for search were pathogenesis of apical periodontitis cytokines, periapical granuloma cytokines, inflammatory infiltrate apical periodontitis. The search was restricted to English language articles, published from 1999 to December 2010. Additionally, a manual search in the cytokine production, cytokine functions and periapical tissue destruction in the journals and books was performed. RESULTS In total, 97 literature sources were obtained and reviewed. The topics covered in this article include cellular composition of an inflammatory infiltrate in the periapical lesions, mechanisms of the formation of the innate and specific immune response. Studies which investigated cytokine secretion and functions were identified and cellular and molecular interactions in the course of apical periodontitis described. CONCLUSIONS The abundance and interactions of various inflammatory and anti-inflammatory molecules can influence and alter the state and progression of the disease. Therefore, periapical inflammatory response offers a model, suited for the study of many facets of pathogenesis, biocompatibility of different materials to periapical tissues and development of novel treatment methods, based on the regulation of cytokines expression.
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Affiliation(s)
- Indre Graunaite
- Department of Dental and Oral Pathology, Faculty of Odontology, Lithuanian University of Health SciencesLithuania.
| | - Greta Lodiene
- Department of Dental and Oral Pathology, Faculty of Odontology, Lithuanian University of Health SciencesLithuania.
| | - Vita Maciulskiene
- Department of Dental and Oral Pathology, Faculty of Odontology, Lithuanian University of Health SciencesLithuania.
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Liao CR, Chang YS, Peng WH, Lai SC, Ho YL. Analgesic and anti-inflammatory activities of the methanol extract of Elaeagnus oldhamii Maxim. in mice. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2012; 40:581-97. [PMID: 22745072 DOI: 10.1142/s0192415x12500449] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2023]
Abstract
We investigated possible mechanisms of analgesic and anti-inflammatory activities of the methanol extract from the leaf of Elaeagnus oldhamii Maxim. (EO(MeOH)). EO(MeOH) was evaluated for its analgesic activity in acetic acid-induced writhing response and formalin test, and anti-inflammatory effect was examined by λ-carrageenan-induced paw edema assay. We detected the activities of GPx, GRd and SOD in the liver, and the levels of inflammatory mediators including IL-1β, IL-6, TNF-α, COX-2, MDA and NO in the edema paw to investigate the mechanism of action against inflammation. Total polyphenol, flavonoid and flavanol contents of EO(MeOH) were detected to explore its antioxidant activities. Results showed that, in the analgesic test, EO(MeOH) decreased acetic acid-induced writhing response and the licking time in the late phase of formalin test. In the anti-inflammatory test, EO(MeOH) decreased paw edema at the 2nd, 3rd, 4th and 5th h after λ-carrageenan had been injected. EO(MeOH) increased the activities of SOD and GPx in liver tissue and decreased MDA, NO, IL-1β, IL-6, TNF-α and COX-2 levels in paw edema tissue at the 3rd h after λ-carrageenan-induced inflammatory reaction. EO(MeOH) exhibited abundant polyphenol, flavonoid and flavanol contents. In HPLC fingerprint test of EO(MeOH), two index ingredients, ursolic acid and pomolic acid, were isolated from EO(MeOH) and were exhibited in HPLC chromatographic analysis. The results demonstrated analgesic and anti-inflammatory effects of EO(MeOH). It was indicated that the anti-inflammatory mechanism of EO(MeOH) may be due to declined levels of NO and MDA in the edema paw through increasing the activities of SOD, GPx and GRd in the liver. Additionally, EO(MeOH) decreased IL-1β, IL-6, TNF-α and COX-2 levels in the edema paw. The results suggested its value in future development of herbal medicine for the treatment of inflammatory diseases.
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Affiliation(s)
- Chi-Ren Liao
- School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung, Taiwan
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Tang Y, Sun F, Li X, Zhou Y, Yin S, Zhou X. Porphyromonas endodontalis Lipopolysaccharides Induce RANKL by Mouse Osteoblast in a Way Different from That of Escherichia coli Lipopolysaccharide. J Endod 2011; 37:1653-8. [DOI: 10.1016/j.joen.2011.08.015] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2011] [Revised: 08/09/2011] [Accepted: 08/09/2011] [Indexed: 01/04/2023]
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Henriques LCF, de Brito LCN, Tavares WLF, Vieira LQ, Ribeiro Sobrinho AP. Cytokine Analysis in Lesions Refractory to Endodontic Treatment. J Endod 2011; 37:1659-62. [DOI: 10.1016/j.joen.2011.08.007] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2011] [Revised: 07/18/2011] [Accepted: 08/02/2011] [Indexed: 11/30/2022]
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Morsani JM, Aminoshariae A, Han YW, Montagnese TA, Mickel A. Genetic predisposition to persistent apical periodontitis. J Endod 2011; 37:455-9. [PMID: 21419289 DOI: 10.1016/j.joen.2011.01.009] [Citation(s) in RCA: 74] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2010] [Revised: 01/13/2011] [Accepted: 01/15/2011] [Indexed: 10/18/2022]
Abstract
INTRODUCTION The proinflammatory cytokine interleukin (IL)-1 is a key regulator of host responses to microbial infection and a major modulator of extracellular matrix catabolism and bone resorption. Allele2 of IL-1β is associated with a four-fold increase in IL-1β production. The aim of this case-control study was to evaluate the gene polymorphism of IL-1β in the pathogenesis of endodontic failure. We hypothesized that the gene polymorphism (allele2 of IL-1β) would influence host response and enhance inflammatory reactions predisposing to persistent apical periodontitis (PAP). MATERIALS AND METHODS Subjects with at least 1 year of follow-up after root canal therapy (RCT) were recalled. Inclusion and exclusion criteria were applied, and 34 subjects with signs/symptoms of PAP with otherwise acceptable RCT were included. Sixty-one controls showed healing with acceptable RCT. Genomic DNA from buccal mucosa was amplified by polymerase chain reaction followed by restriction fragment length polymorphism to distinguish the alleles of IL-1β gene polymorphism. RESULTS A significant difference in the distribution of the polymorphic genotype among cases (70.6%) and controls (24.6%) (P < .001, Pearson χ(2)) was shown. CONCLUSIONS These findings suggest that specific genetic markers associated with increased IL-1β production may contribute to increased susceptibility to PAP.
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Affiliation(s)
- Jussara M Morsani
- American Board of Endodontics, Case Western Reserve School of Dental Medicine, Cleveland, Ohio, USA
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Bałkowiec-Iskra E, Vermehren-Schmaedick A, Balkowiec A. Tumor necrosis factor-α increases brain-derived neurotrophic factor expression in trigeminal ganglion neurons in an activity-dependent manner. Neuroscience 2011; 180:322-33. [PMID: 21335064 PMCID: PMC3070813 DOI: 10.1016/j.neuroscience.2011.02.028] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2010] [Revised: 01/20/2011] [Accepted: 02/10/2011] [Indexed: 01/19/2023]
Abstract
Many chronic trigeminal pain conditions, such as migraine or temporo-mandibular disorders, are associated with inflammation within peripheral endings of trigeminal ganglion (TG) sensory neurons. A critical role in mechanisms of neuroinflammation is attributed to proinflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α (TNFα) that also contribute to mechanisms of persistent neuropathic pain resulting from nerve injury. However, the mechanisms of cytokine-mediated synaptic plasticity and nociceptor sensitization are not completely understood. In the present study, we examined the effects of TNFα on neuronal expression of brain-derived neurotrophic factor (BDNF), whose role in synaptic plasticity and sensitization of nociceptive pathways is well documented. We show that 4- and 24-h treatment with TNFα increases BDNF mRNA and protein, respectively, in neuron-enriched dissociated cultures of rat TG. TNFα increases the phosphorylated form of the cyclic AMP-responsive element binding protein (CREB), a transcription factor involved in regulation of BDNF expression in neurons, and activates transcription of BDNF exon IV (former exon III) and, to a lesser extent, exon VI (former exon IV), but not exon I. TNFα-mediated increase in BDNF expression is accompanied by increase in calcitonin gene-related peptide (CGRP), which is consistent with previously published studies, and indicates that both peptides are similarly regulated in TG neurons by inflammatory mediators. The effect of TNFα on BDNF expression is dependent on sodium influx through TTX-sensitive channels and on p38-mitogen-activated protein kinase. Moreover, electrical stimulation and forskolin, known to increase intracellular cAMP, potentiate the TNFα-mediated upregulation of BDNF expression. This study provides new evidence for a direct action of proinflammatory cytokines on TG primary sensory neurons, and reveals a mechanism through which TNFα stimulates de novo synthesis of BDNF in these neurons. Thus, TNFα should be considered in mechanisms of BDNF-dependent neuronal plasticity.
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Affiliation(s)
- Ewa Bałkowiec-Iskra
- Department of Integrative Biosciences, Oregon Health & Science University School of Dentistry, Portland, Oregon
- Department of Experimental & Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland
| | - Anke Vermehren-Schmaedick
- Department of Integrative Biosciences, Oregon Health & Science University School of Dentistry, Portland, Oregon
| | - Agnieszka Balkowiec
- Department of Integrative Biosciences, Oregon Health & Science University School of Dentistry, Portland, Oregon
- Department of Physiology & Pharmacology, Oregon Health & Science University School of Medicine, Portland, Oregon
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