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Mei EH, Yao C, Chen YN, Nan SX, Qi SC. Multifunctional role of oral bacteria in the progression of non-alcoholic fatty liver disease. World J Hepatol 2024; 16:688-702. [PMID: 38818294 PMCID: PMC11135273 DOI: 10.4254/wjh.v16.i5.688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 02/26/2024] [Accepted: 04/07/2024] [Indexed: 05/22/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders of varying severity, ultimately leading to fibrosis. This spectrum primarily consists of NAFL and non-alcoholic steatohepatitis. The pathogenesis of NAFLD is closely associated with disturbances in the gut microbiota and impairment of the intestinal barrier. Non-gut commensal flora, particularly bacteria, play a pivotal role in the progression of NAFLD. Notably, Porphyromonas gingivalis, a principal bacterium involved in periodontitis, is known to facilitate lipid accumulation, augment immune responses, and induce insulin resistance, thereby exacerbating fibrosis in cases of periodontitis-associated NAFLD. The influence of oral microbiota on NAFLD via the "oral-gut-liver" axis is gaining recognition, offering a novel perspective for NAFLD management through microbial imbalance correction. This review endeavors to encapsulate the intricate roles of oral bacteria in NAFLD and explore underlying mechanisms, emphasizing microbial control strategies as a viable therapeutic avenue for NAFLD.
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Affiliation(s)
- En-Hua Mei
- Shanghai Medical College, Fudan University, Shanghai 200000, China
- Department of Prothodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai 200000, China
- Shanghai Key Laboratory of Craniomaxiofacial Development and Diseases, Fudan University, Shanghai 200000, China
| | - Chao Yao
- Department of Prothodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai 200000, China
- Shanghai Key Laboratory of Craniomaxiofacial Development and Diseases, Fudan University, Shanghai 200000, China
| | - Yi-Nan Chen
- Shanghai Medical College, Fudan University, Shanghai 200000, China
| | - Shun-Xue Nan
- Shanghai Medical College, Fudan University, Shanghai 200000, China
| | - Sheng-Cai Qi
- Department of Prothodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai 200000, China
- Shanghai Key Laboratory of Craniomaxiofacial Development and Diseases, Fudan University, Shanghai 200000, China.
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Kuraji R, Ye C, Zhao C, Gao L, Martinez A, Miyashita Y, Radaic A, Kamarajan P, Le C, Zhan L, Range H, Sunohara M, Numabe Y, Kapila YL. Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis. NPJ Biofilms Microbiomes 2024; 10:3. [PMID: 38233485 PMCID: PMC10794237 DOI: 10.1038/s41522-024-00476-x] [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: 04/17/2023] [Accepted: 01/02/2024] [Indexed: 01/19/2024] Open
Abstract
Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice. In the context of disease, nisin treatment significantly shifted the microbiome towards a new composition, commensurate with health while preventing the harmful inflammation in the small intestine concomitant with decreased villi structural integrity, and heightened hepatic exposure to bacteria and lipid and malondialdehyde accumulation in the liver. Validation with RNA Seq analyses, confirmed the significant infection-related alteration of several genes involved in mitochondrial dysregulation, oxidative phosphorylation, and metal/iron binding and their restitution following nisin treatment. In support of these in vivo findings indicating that periodontopathogens induce gastrointestinal and liver distant organ lesions, human autopsy specimens demonstrated a correlation between tooth loss and severity of liver disease. Nisin's ability to shift the gut and liver microbiome towards a new state commensurate with health while mitigating enteritis, represents a novel approach to treating NAFLD-steatohepatitis-associated periodontal disease.
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Affiliation(s)
- Ryutaro Kuraji
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Changchang Ye
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Periodontology, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Chuanjiang Zhao
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- Department of Periodontology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Li Gao
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- Department of Periodontology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - April Martinez
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
| | - Yukihiro Miyashita
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Allan Radaic
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- Sections of Biosystems and Function and Periodontics, School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA
| | - Pachiyappan Kamarajan
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- Sections of Biosystems and Function and Periodontics, School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA
| | - Charles Le
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
| | - Ling Zhan
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
| | - Helene Range
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- Department of Periodontology, University of Rennes, UFR of Odontology; Service d'Odontologie, CHU de Rennes, Rennes, France
- INSERM CHU Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer); CIC 1414, Rennes, France
| | - Masataka Sunohara
- Department of Anatomy, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Yukihiro Numabe
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Yvonne L Kapila
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA.
- Sections of Biosystems and Function and Periodontics, School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA.
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Joo JY, Park HR, Cho Y, Noh Y, Lee CH, Lee SG. Increased prevalence of periodontitis with hypouricemic status: findings from the Korean National Health and Nutrition Examination Survey, 2016-2018. J Periodontal Implant Sci 2023; 53:283-294. [PMID: 36731863 PMCID: PMC10465814 DOI: 10.5051/jpis.2202220111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 10/06/2022] [Accepted: 11/08/2022] [Indexed: 02/04/2023] Open
Abstract
PURPOSE The aim of this study was to investigate the relationship between serum uric acid (SUA) levels and the risk of periodontitis in Korean adults using data from the Korean National Health and Nutrition Examination Survey (KNHANES). METHODS This cross-sectional study used data from the KNHANES 2016-2018 and analysed 12,735 Korean adults aged ≥19 years who underwent oral examinations. Hypouricemia was defined as SUA <3 mg/dL in men and <2 mg/dL in women, and hyperuricemia was defined as SUA ≥7 mg/dL in men and ≥6 mg/dL in women. RESULTS The weighted prevalence of hypouricemia and hyperuricemia was 0.6% and 12.9%, respectively. The overall weighted periodontitis rate was 30.5%. The frequency of periodontitis in subjects with hypouricemia, normouricemia, and hyperuricemia were 51.1%, 30.3%, and 30.6%, respectively. Study participants with hypouricemia were significantly older, had significantly fasting blood glucose levels, and had better kidney function than non-hypouricemic participants. In univariate logistic regression analyses, hypouricemia was associated with periodontitis, but hyperuricemia was not. The fully adjusted model revealed that the adjusted odds ratio of hypouricemia for periodontitis was 1.62 (95% confidence interval, 1.13-2.33), while the relationship between hyperuricemia and periodontitis in the multivariable logistic regression model was not significant. CONCLUSIONS The results of this study suggest that hypouricemia is associated with an increased risk of periodontitis.
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Affiliation(s)
- Ji-Young Joo
- Department of Periodontology, Dental Research Institute, Pusan National University Dental Hospital, Yangsan, Korea
- Periodontal Disease Signaling Network Research Center, Dental and Life Science Institute, Pusan National University School of Dentistry, Yangsan, Korea
| | - Hae Ryoun Park
- Periodontal Disease Signaling Network Research Center, Dental and Life Science Institute, Pusan National University School of Dentistry, Yangsan, Korea
- Department of Oral Pathology, Pusan National University School of Dentistry, Yangsan, Korea
| | - Youngseuk Cho
- Department of Statistics, Pusan National University College of Natural Sciences, Busan, Korea
| | - Yunhwan Noh
- Department of Statistics, Pusan National University College of Natural Sciences, Busan, Korea
| | - Chang Hun Lee
- Department of Pathology, Pusan National University School of Medicine, Busan, Korea
| | - Seung-Geun Lee
- Department of Internal Medicine, Pusan National University School of Medicine and Pusan National University Hospital, Busan, Korea.
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Kuraji R, Shiba T, Dong TS, Numabe Y, Kapila YL. Periodontal treatment and microbiome-targeted therapy in management of periodontitis-related nonalcoholic fatty liver disease with oral and gut dysbiosis. World J Gastroenterol 2023; 29:967-996. [PMID: 36844143 PMCID: PMC9950865 DOI: 10.3748/wjg.v29.i6.967] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Revised: 11/14/2022] [Accepted: 01/30/2023] [Indexed: 02/10/2023] Open
Abstract
A growing body of evidence from multiple areas proposes that periodontal disease, accompanied by oral inflammation and pathological changes in the microbiome, induces gut dysbiosis and is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). A subgroup of NAFLD patients have a severely progressive form, namely nonalcoholic steatohepatitis (NASH), which is characterized by histological findings that include inflammatory cell infiltration and fibrosis. NASH has a high risk of further progression to cirrhosis and hepatocellular carcinoma. The oral microbiota may serve as an endogenous reservoir for gut microbiota, and transport of oral bacteria through the gastro-intestinal tract can set up a gut microbiome dysbiosis. Gut dysbiosis increases the production of potential hepatotoxins, including lipopolysaccharide, ethanol, and other volatile organic compounds such as acetone, phenol and cyclopentane. Moreover, gut dysbiosis increases intestinal permeability by disrupting tight junctions in the intestinal wall, leading to enhanced translocation of these hepatotoxins and enteric bacteria into the liver through the portal circulation. In particular, many animal studies support that oral administration of Porphyromonas gingivalis, a typical periodontopathic bacterium, induces disturbances in glycolipid metabolism and inflammation in the liver with gut dysbiosis. NAFLD, also known as the hepatic phenotype of metabolic syndrome, is strongly associated with metabolic complications, such as obesity and diabetes. Periodontal disease also has a bidirectional relationship with metabolic syndrome, and both diseases may induce oral and gut microbiome dysbiosis with insulin resistance and systemic chronic inflammation cooperatively. In this review, we will describe the link between periodontal disease and NAFLD with a focus on basic, epidemiological, and clinical studies, and discuss potential mechanisms linking the two diseases and possible therapeutic approaches focused on the microbiome. In conclusion, it is presumed that the pathogenesis of NAFLD involves a complex crosstalk between periodontal disease, gut microbiota, and metabolic syndrome. Thus, the conventional periodontal treatment and novel microbiome-targeted therapies that include probiotics, prebiotics and bacteriocins would hold great promise for preventing the onset and progression of NAFLD and subsequent complications in patients with periodontal disease.
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Affiliation(s)
- Ryutaro Kuraji
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo 102-0071, Japan
- Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA 94143, United States
| | - Takahiko Shiba
- Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, United States
- Department of Periodontology, Tokyo Medical and Dental University, Tokyo 113-8549, Japan
| | - Tien S Dong
- The Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Department of Medicine, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
| | - Yukihiro Numabe
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo 102-8159, Japan
| | - Yvonne L Kapila
- Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA 94143, United States
- Sections of Biosystems and Function and Periodontics, Professor and Associate Dean of Research, Felix and Mildred Yip Endowed Chair in Dentistry, University of California Los Angeles, Los Angeles, CA 90095, United States
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Oliveira MOA, Leonço ÁR, Pavani VB, Barbosa IR, Campos MM. Omega-3 Effects on Ligature-Induced Periodontitis in Rats with Fructose-Induced Metabolic Syndrome. Inflammation 2023; 46:388-403. [PMID: 36171491 DOI: 10.1007/s10753-022-01741-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 09/05/2022] [Accepted: 09/14/2022] [Indexed: 11/05/2022]
Abstract
Both periodontal disease (PD) and metabolic syndrome (MS) represent disorders of concern worldwide. Current evidence indicates that PD and MS might negatively influence each other, increasing the risk for cardiovascular diseases (CVD), via mutual inflammatory pathways. A failure of the inflammation resolution mechanisms is crucial for these comorbidities. Fish oil-derived omega-3 has been linked with resolution-driven responses in different pathological conditions during the last years. This study evaluated the impacts of omega-3 supplementation in a rat model combining ligature-induced PD and 10% fructose intake-elicited MS. Our main findings show that 10% fructose ingestion led to an elevation of Lee index and white adipose tissue (WAT) weight, along with hepatic alterations, accompanied by an increase of leptin, and a decrement of adiponectin serum amounts, regardless of PD induction. Noteworthy, the co-induction of PD and MS resulted in higher levels of glycemia and triglycerides, being this latter effect lessened by omega-3 supplementation. In this case, the beneficial effects of omega-3 might be associated with its ability to recover the decline of serum adiponectin levels in rats with PD plus MS. As expected, PD induction led to alveolar bone loss, independent of MS induction. However, the supplementation with omega-3 restored alveolar bone in PD control animals, but not in the rats with PD combined with MS. Our study extends the knowledge about PD and MS as comorbidities, showing novel effects of omega-3 supplementation in this context.
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Affiliation(s)
- Maysa O A Oliveira
- Programa de Pós-Graduação em Biologia Celular e Molecular, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil
- Centro de Pesquisa em Toxicologia e Farmacologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Álvaro R Leonço
- Centro de Pesquisa em Toxicologia e Farmacologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil
- Curso de Graduação em Medicina, Escola de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Vinícius B Pavani
- Curso de Graduação em Odontologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, Partenon, Porto Alegre, RS, 90619-900, Brazil
| | - Isadora R Barbosa
- Programa de Pós-Graduação em Biologia Celular e Molecular, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil
- Centro de Pesquisa em Toxicologia e Farmacologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Maria M Campos
- Programa de Pós-Graduação em Biologia Celular e Molecular, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
- Centro de Pesquisa em Toxicologia e Farmacologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
- Curso de Graduação em Odontologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, Partenon, Porto Alegre, RS, 90619-900, Brazil.
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Kamata Y, Kessoku T, Shimizu T, Sato S, Kobayashi T, Kurihashi T, Morozumi T, Iwasaki T, Takashiba S, Hatanaka K, Hamada N, Kodama T, Higurashi T, Taguri M, Yoneda M, Usuda H, Wada K, Nakajima A, Minabe M. Periodontal Treatment and Usual Care for Nonalcoholic Fatty Liver Disease: A Multicenter, Randomized Controlled Trial. Clin Transl Gastroenterol 2022; 13:e00520. [PMID: 36000999 PMCID: PMC10476832 DOI: 10.14309/ctg.0000000000000520] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 07/06/2022] [Indexed: 01/31/2023] Open
Abstract
INTRODUCTION Periodontal disease is associated with nonalcoholic fatty liver disease (NAFLD). We evaluated periodontal treatment efficacy in patients with NAFLD and periodontal disease. METHODS This multicenter, 2-arm, randomized study recruited adult patients with NAFLD and periodontitis, alanine aminotransferase levels ≥40 U/L, and equivalent steatosis grade ≥1. Forty eligible patients (18 men and 22 women) were randomly assigned to 2 groups (scaling and root planning [SRP; n = 20] and tooth brushing [n = 20] groups) stratified by age and sex. The primary and secondary endpoints were changes in alanine aminotransferase levels and serum Porphyromonas gingivalis IgG antibody titers from baseline to 12 weeks, respectively. Efficacy analysis was performed using an intention-to-treat approach ( t test). This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000022079). RESULTS We observed a significantly higher decrease in absolute alanine aminotransferase levels and P. gingivalis IgG antibody titers in the SRP group than in the tooth brushing group (-12 vs 1 U/L; mean difference [δ], -12; 95% confidence interval [CI], -20 to -5; P = 0.002). The decrease in P. gingivalis IgG antibody titer was significantly higher in the SRP group than in the tooth brushing group (FDC381, -1.6 [2.5]; δ, -1.6; 95% CI, -2.7 to -0.4; P = 0.0092; SU63, -1.7 [2.0]; δ, -1.7; 95% CI, -2.7 to -0.7). No life-threatening events or treatment-related deaths occurred. DISCUSSION Periodontal treatment induced significant short-term and mid-term reductions in liver enzyme levels and antibody titers. Further research is warranted to clearly define SRP efficacy and tolerability in patients with NAFLD and periodontitis.
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Affiliation(s)
- Yohei Kamata
- Department of Highly Advanced Oral Stomatology, Yokohama Clinic, Kanagawa Dental University, Yokohama, Japan
| | - Takaomi Kessoku
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Tomoko Shimizu
- Department of Highly Advanced Oral Stomatology, Yokohama Clinic, Kanagawa Dental University, Yokohama, Japan
| | - Satsuki Sato
- Department of Highly Advanced Oral Stomatology, Yokohama Clinic, Kanagawa Dental University, Yokohama, Japan
| | - Takashi Kobayashi
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Takeo Kurihashi
- Department of Internal Medicine, Yokohama Clinic, Kanagawa Dental University, Yokohama, Japan
| | - Toshiya Morozumi
- Division of Periodontology, Department of Oral Interdisciplinary Medicine, Graduate School of Dentistry, Kanagawa Dental University, Yokosuka, Japan
| | - Tomoyuki Iwasaki
- Iwasaki Internal Medicine Clinic, Kamihoshikawa, Hodogaya-ku, Yokohama, Japan
| | - Shogo Takashiba
- Department of Pathophysiology—Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Kazu Hatanaka
- Department of Pathophysiology—Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Nobushiro Hamada
- Division of Microbiology, Department of Oral Science Graduate School of Dentistry, Kanagawa Dental University, Yokosuka, Japan
| | - Toshiro Kodama
- Department of Implantology and Periodontology, Graduate School of Dentistry, Kanagawa Dental University, Yokohama, Japan
| | - Takuma Higurashi
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Masataka Taguri
- Department of Biostatistics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Haruki Usuda
- Department of Pharmacology, Shimane University School of Medicine, Shimane, Japan
| | - Koichiro Wada
- Department of Pharmacology, Shimane University School of Medicine, Shimane, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Masato Minabe
- Division of Periodontology, Department of Oral Interdisciplinary Medicine, Graduate School of Dentistry, Kanagawa Dental University, Yokosuka, Japan
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Kuraji R, Kapila Y, Numabe Y. Periodontal Disease and Nonalcoholic Fatty Liver Disease: New Microbiome-Targeted Therapy Based on the Oral–Gut–Liver Axis Concept. CURRENT ORAL HEALTH REPORTS 2022; 9:89-102. [DOI: 10.1007/s40496-022-00312-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 04/26/2022] [Indexed: 01/03/2025]
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Kuraji R, Sekino S, Kapila Y, Numabe Y. Periodontal disease-related nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: An emerging concept of oral-liver axis. Periodontol 2000 2021; 87:204-240. [PMID: 34463983 PMCID: PMC8456799 DOI: 10.1111/prd.12387] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Periodontal disease, a chronic inflammatory disease of the periodontal tissues, is not only a major cause of tooth loss, but it is also known to exacerbate/be associated with various metabolic disorders, such as obesity, diabetes, dyslipidemia, and cardiovascular disease. Recently, growing evidence has suggested that periodontal disease has adverse effects on the pathophysiology of liver disease. In particular, nonalcoholic fatty liver disease, a hepatic manifestation of metabolic syndrome, has been associated with periodontal disease. Nonalcoholic fatty liver disease is characterized by hepatic fat deposition in the absence of a habitual drinking history, viral infections, or autoimmune diseases. A subset of nonalcoholic fatty liver diseases can develop into more severe and progressive forms, namely nonalcoholic steatohepatitis. The latter can lead to cirrhosis and hepatocellular carcinoma, which are end‐stage liver diseases. Extensive research has provided plausible mechanisms to explain how periodontal disease can negatively affect nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, namely via hematogenous or enteral routes. During periodontitis, the liver is under constant exposure to various pathogenic factors that diffuse systemically from the oral cavity, such as bacteria and their by‐products, inflammatory cytokines, and reactive oxygen species, and these can be involved in disease promotion of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Also, gut microbiome dysbiosis induced by enteral translocation of periodontopathic bacteria may impair gut wall barrier function and promote the transfer of hepatotoxins and enterobacteria to the liver through the enterohepatic circulation. Moreover, in a population with metabolic syndrome, the interaction between periodontitis and systemic conditions related to insulin resistance further strengthens the association with nonalcoholic fatty liver disease. However, most of the pathologic links between periodontitis and nonalcoholic fatty liver disease in humans are provided by epidemiologic observational studies, with the causal relationship not yet being established. Several systematic and meta‐analysis studies also show conflicting results. In addition, the effect of periodontal treatment on nonalcoholic fatty liver disease has hardly been studied. Despite these limitations, the global burden of periodontal disease combined with the recent nonalcoholic fatty liver disease epidemic has important clinical and public health implications. Emerging evidence suggests an association between periodontal disease and liver diseases, and thus we propose the term periodontal disease–related nonalcoholic fatty liver disease or periodontal disease–related nonalcoholic steatohepatitis. Continued efforts in this area will pave the way for new diagnostic and therapeutic approaches based on a periodontologic viewpoint to address this life‐threatening liver disease.
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Affiliation(s)
- Ryutaro Kuraji
- Department of Life Science Dentistry, The Nippon Dental University, Tokyo, Japan.,Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan.,Department of Orofacial Sciences, University of California San Francisco School of Dentistry, San Francisco, California, USA
| | - Satoshi Sekino
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Yvonne Kapila
- Department of Orofacial Sciences, University of California San Francisco School of Dentistry, San Francisco, California, USA
| | - Yukihiro Numabe
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
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Son YJ, Jung DS, Shin JM, Erdenebileg S, Nho CW. Heracleum dissectum Ledeb. ethanol extract attenuates metabolic syndrome symptoms in high-fat diet-induced obese mice by activating adiponectin/AMPK signaling. J Funct Foods 2021. [DOI: 10.1016/j.jff.2021.104581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
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10
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Marcano R, Rojo MÁ, Cordoba-Diaz D, Garrosa M. Pathological and Therapeutic Approach to Endotoxin-Secreting Bacteria Involved in Periodontal Disease. Toxins (Basel) 2021; 13:533. [PMID: 34437404 PMCID: PMC8402370 DOI: 10.3390/toxins13080533] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 07/26/2021] [Indexed: 12/16/2022] Open
Abstract
It is widely recognized that periodontal disease is an inflammatory entity of infectious origin, in which the immune activation of the host leads to the destruction of the supporting tissues of the tooth. Periodontal pathogenic bacteria like Porphyromonas gingivalis, that belongs to the complex net of oral microflora, exhibits a toxicogenic potential by releasing endotoxins, which are the lipopolysaccharide component (LPS) available in the outer cell wall of Gram-negative bacteria. Endotoxins are released into the tissues causing damage after the cell is lysed. There are three well-defined regions in the LPS: one of them, the lipid A, has a lipidic nature, and the other two, the Core and the O-antigen, have a glycosidic nature, all of them with independent and synergistic functions. Lipid A is the "bioactive center" of LPS, responsible for its toxicity, and shows great variability along bacteria. In general, endotoxins have specific receptors at the cells, causing a wide immunoinflammatory response by inducing the release of pro-inflammatory cytokines and the production of matrix metalloproteinases. This response is not coordinated, favoring the dissemination of LPS through blood vessels, as well as binding mainly to Toll-like receptor 4 (TLR4) expressed in the host cells, leading to the destruction of the tissues and the detrimental effect in some systemic pathologies. Lipid A can also act as a TLRs antagonist eliciting immune deregulation. Although bacterial endotoxins have been extensively studied clinically and in a laboratory, their effects on the oral cavity and particularly on periodontium deserve special attention since they affect the connective tissue that supports the tooth, and can be linked to advanced medical conditions. This review addresses the distribution of endotoxins associated with periodontal pathogenic bacteria and its relationship with systemic diseases, as well as the effect of some therapeutic alternatives.
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Affiliation(s)
- Rosalia Marcano
- Department of Cell Biology, Histology and Pharmacology, Faculty of Medicine and INCYL, University of Valladolid, 47005 Valladolid, Spain;
| | - M. Ángeles Rojo
- Area of Experimental Sciences, Miguel de Cervantes European University, 47012 Valladolid, Spain;
| | - Damián Cordoba-Diaz
- Area of Pharmaceutics and Food Technology, Faculty of Pharmacy, and IUFI, Complutense University of Madrid, 28040 Madrid, Spain;
| | - Manuel Garrosa
- Department of Cell Biology, Histology and Pharmacology, Faculty of Medicine and INCYL, University of Valladolid, 47005 Valladolid, Spain;
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11
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Chen ZY, Xu TT, Liang ZJ, Zhao L, Xiong XQ, Xie KK, Yu WX, Zeng XW, Gao J, Zhou YH, Luo G, Yu T. Untargeted and targeted gingival metabolome in rodents reveal metabolic links between high-fat diet-induced obesity and periodontitis. J Clin Periodontol 2021; 48:1137-1148. [PMID: 33998036 DOI: 10.1111/jcpe.13486] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 04/19/2021] [Accepted: 04/27/2021] [Indexed: 12/19/2022]
Abstract
AIM To characterize gingival metabolome in high-fat diet (HFD)-induced obesity in mice with/without periodontitis. METHODS HFD-induced obesity mouse model was established by 16-week feeding, and a lean control group was fed with low-fat diet (n = 21/group). Both models were induced for periodontitis on the left sides by molar ligation for 10 days, whereas the right sides were used as controls. Gingival metabolome and arginine metabolism were analysed by non-targeted/targeted liquid chromatography-mass spectrometry. RESULTS Of 2247 reference features, presence of periodontitis altered 165 in lean versus 885 in HFD mice; and HFD altered 525 in absence versus 1435 in presence of periodontitis. Compared with healthy condition, periodontitis and HFD had distinct effects on gingival metabolome. Metabolomic impacts of periodontitis were generally greater in HFD mice versus lean controls. K-medoids clustering showed that HFD amplified the impacts of periodontitis on gingival metabolome in both intensity and extensity. Ten metabolic pathways were enriched, including 2 specific to periodontitis, 5 specific to HFD and 3 shared ones. Targeted validation on arginine metabolism confirmed the additive effects between HFD and periodontitis. CONCLUSION The obese population consuming excessive HFD display amplified metabolic response to periodontitis, presenting a metabolic susceptibility to exacerbated periodontal destruction.
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Affiliation(s)
- Zi-Yun Chen
- Department of Periodontics, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Tian-Tian Xu
- Department of Periodontics, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Zhao-Jia Liang
- Department of Periodontics, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Li Zhao
- Department of Prosthodontics, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Xiao-Qin Xiong
- Department of Periodontics, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Kun-Ke Xie
- Department of Periodontics, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Wan-Xin Yu
- Department of Periodontics, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Xiao-Wen Zeng
- Department of Periodontics, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Jie Gao
- Department of Periodontics, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Ying-Hong Zhou
- Department of Periodontics, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.,Queensland University of Technology, Centre for Biomedical Technologies, Queensland, Australia
| | - Gang Luo
- Department of Periodontics, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Ting Yu
- Department of Periodontics, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
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12
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Tokoro M, Gotoh K, Kudo Y, Hirashita Y, Iwao M, Arakawa M, Endo M, Oribe J, Masaki T, Honda K, Kakuma T, Seike M, Murakami K, Shibata H. α-Tocopherol suppresses hepatic steatosis by increasing CPT-1 expression in a mouse model of diet-induced nonalcoholic fatty liver disease. Obes Sci Pract 2021; 7:91-99. [PMID: 33680496 PMCID: PMC7909598 DOI: 10.1002/osp4.460] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 09/29/2020] [Accepted: 09/30/2020] [Indexed: 12/12/2022] Open
Abstract
Aim Antioxidant therapy for with vitamin E appears to be effective for the treatment of nonalcoholic fatty liver disease (NAFLD). However, the mechanism of action and optimal therapeutic dosage is unclear. The present study was undertaken to examine whether the effects of α‐tocopherol (α‐Toc) on NAFLD are dose‐dependent in a diet‐induced obese model. Methods Male mice were fed standard chow, high‐fat (HF) diet, HF diet with low‐dose, or with high dose of α‐Toc supplementation. Histological findings, triglyceride content, and the levels of protein expression related to fatty acid synthesis/oxidation such as carnitine palmitoyltransferase I (CPT‐1) of liver were evaluated. In addition, 2‐tetradecylglycidic acid (TDGA), a CPT‐1 inhibitor, was administered to mice fed HF diet with low‐dose of α‐Toc. Finally, HepG2 cells in fat‐loaded environment were treated with 0–50 μM α‐Toc. Results Treatment of low‐dose of α‐Toc decreased HF‐induced hepatic fat accumulation, but this finding was not observed in treatment of high dose of α‐Toc. HF‐induced reduction of CPT‐1 was attenuated with low‐dose of α‐Toc but not with high dose of α‐Toc. TDGA suppressed the improvement of histological findings in liver induced by low‐dose of α‐Toc treatment. CPT‐1 expression in HepG2 cells increased in response to low‐dose of α‐Toc, but not in high dose. Conclusions Dual action of α‐Toc on CPT‐1 protein levels was observed. The effect of vitamin E on NAFLD may be not be dose‐dependent.
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Affiliation(s)
- Masanori Tokoro
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology Faculty of Medicine Oita University Oita Japan.,Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Koro Gotoh
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology Faculty of Medicine Oita University Oita Japan
| | - Yoko Kudo
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Yuka Hirashita
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Masao Iwao
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Mie Arakawa
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Mizuki Endo
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Junya Oribe
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Takayuki Masaki
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology Faculty of Medicine Oita University Oita Japan
| | - Koichi Honda
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Tetsuya Kakuma
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology Faculty of Medicine Oita University Oita Japan
| | - Masataka Seike
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Kazunari Murakami
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Hirotaka Shibata
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology Faculty of Medicine Oita University Oita Japan
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13
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Yamamoto K, Ikeya T, Okuyama S, Fukuda K, Kobayashi D. Association between the Frequency of Daily Toothbrushing and Development of Nonalcoholic Fatty Liver Disease. Dig Dis 2021; 39:646-652. [PMID: 33535206 DOI: 10.1159/000514930] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 01/22/2021] [Indexed: 02/02/2023]
Abstract
UNLABELLED Background & Aim: This study aimed to evaluate the association between the frequency of daily toothbrushing and the development of nonalcoholic fatty liver disease (NAFLD). METHODS A retrospective longitudinal study was conducted from 2005 to 2012 at the Center for Preventive Medicine at St. Luke's International Hospital, Japan. Data on all participants who underwent a health checkup during the study period were collected. NAFLD was diagnosed by abdominal ultrasonography, and all participants who were diagnosed with NAFLD at the time of their initial visit, consumed alcohol in any amount, or had received only one health checkup were excluded. The questionnaire for the frequency of daily toothbrushing was conducted as part of health checkups. The primary outcome was the risk of developing NAFLD according to the frequency of daily toothbrushing (1-2 times a day or 3 times a day) compared to those who brush teeth once or less than once a day. RESULTS Data were collected from 25,804 people. A total of 3,289 (12.7%) participants developed NAFLD. The mean age was 45.2 years, and 6,901 (26.7%) of the participants were male. The risk of developing NAFLD significantly decreased with increased frequency of daily toothbrushing. Adjusted odds ratios (ORs) are as follows: brushing teeth 1-2 times a day (OR: 0.85, 95% confidence interval [CI]: 0.77-0.95) and 3 times a day (OR: 0.74, 95% CI: 0.67-0.82). CONCLUSION Frequent toothbrushing was shown to significantly reduce the risk of developing NAFLD.
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Affiliation(s)
- Kazuki Yamamoto
- Department of Gastroenterology, St. Luke's International Hospital, Tokyo, Japan
| | - Takashi Ikeya
- Department of Gastroenterology, St. Luke's International Hospital, Tokyo, Japan
| | - Shuhei Okuyama
- Department of Gastroenterology, St. Luke's International Hospital, Tokyo, Japan
| | - Katsuyuki Fukuda
- Department of Gastroenterology, St. Luke's International Hospital, Tokyo, Japan
| | - Daiki Kobayashi
- Department of Medicine, St. Luke's International Hospital, Tokyo, Japan.,Department of Epidemiology, St. Luke's Graduate School of Public Health, Tokyo, Japan.,Department of Medicine, Fujita Health University, Toyoake, Japan
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14
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Epsley S, Tadros S, Farid A, Kargilis D, Mehta S, Rajapakse CS. The Effect of Inflammation on Bone. Front Physiol 2021; 11:511799. [PMID: 33584321 PMCID: PMC7874051 DOI: 10.3389/fphys.2020.511799] [Citation(s) in RCA: 120] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 11/30/2020] [Indexed: 12/21/2022] Open
Abstract
Bone remodeling is the continual process to renew the adult skeleton through the sequential action of osteoblasts and osteoclasts. Nuclear factor RANK, an osteoclast receptor, and its ligand RANKL, expressed on the surface of osteoblasts, result in coordinated control of bone remodeling. Inflammation, a feature of illness and injury, plays a distinct role in skewing this process toward resorption. It does so via the interaction of inflammatory mediators and their related peptides with osteoblasts and osteoclasts, as well as other immune cells, to alter the expression of RANK and RANKL. Such chemical mediators include TNFα, glucocorticoids, histamine, bradykinin, PGE2, systemic RANKL from immune cells, and interleukins 1 and 6. Conditions, such as periodontal disease and alveolar bone erosion, aseptic prosthetic loosening, rheumatoid arthritis, and some sports related injuries are characterized by the result of this process. A thorough understanding of bone response to injury and disease, and ability to detect such biomarkers, as well as imaging to identify early structural and mechanical property changes in bone architecture, is important in improving management and outcomes of bone related pathology. While gut health and vitamin and mineral availability appear vitally important, nutraceuticals also have an impact on bone health. To date most pharmaceutical intervention targets inflammatory cytokines, although strategies to favorably alter inflammation induced bone pathology are currently limited. Further research is required in this field to advance early detection and treatments.
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Affiliation(s)
- Scott Epsley
- Philadelphia 76ers, Philadelphia, PA, United States
| | - Samuel Tadros
- Department of Radiology and Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States
| | - Alexander Farid
- Department of Radiology and Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States
| | - Daniel Kargilis
- Department of Radiology and Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States
| | | | - Chamith S. Rajapakse
- Department of Radiology and Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States
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15
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Kuraji R, Wu YH, Hashimoto S, Miyashita Y, Mishiro S, Ito H, Kamarajan P, Kapila Y, Numabe Y. Periodontal inflammation triggers a site-specific and wide radius of calcium metabolic effects on alveolar bone. J Periodontal Res 2020; 56:314-329. [PMID: 33314132 DOI: 10.1111/jre.12824] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 09/30/2020] [Accepted: 10/28/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND OBJECTIVE There is a close relationship between inflammation and bone remodeling in the periodontium. However, previous studies have not delineated the alterations in calcium (Ca) metabolism during periodontitis progression. The aim of this current investigation was to examine Ca dynamics in alveolar bone of rats during progression of ligature-induced periodontal inflammation by using 45 Ca, which is an index of hard tissue neogenesis. MATERIAL AND METHODS To induce periodontitis, the maxillary right first molar (M1) of 8-week-old male rats was ligated with a silk suture for 1, 3, 7, and 28 days. The left M1 was not ligated as a control. To evaluate resultant changes in bone neogenesis, 45 CaCl2 was injected intraperitoneally 24 hours before euthanasia. The left-and-right palatal mucosa, molar teeth (M1 and M2), and alveolar bone were harvested for evaluation of 45 Ca radioactivity using a liquid scintillation counter. The distribution of 45 Ca in maxillary tissues was evaluated using autoradiography (ARG). In addition, we analyzed the bone volume fraction (BV/TV) and bone mineral density (BMD) of the alveolar bone by micro-computed tomography. To investigate the number of osteoclasts and osteoblasts, tartrate-resistant acid phosphatase (TRAP) and bone-specific alkaline phosphatase (BAP) were measured by an enzymatic assay and immunohistochemistry, respectively. RESULTS 45 Ca radioactivity in the alveolar bone of the ligature side decreased by 8% compared to the unligated control-side on day 1, whereas on day 7, it markedly increased by 33%. The 45 Ca levels in the gingival tissue and molar teeth were slightly but significantly lower than the control-side on day 1 and higher from day 3 to 28. The variation in 45 Ca levels for the alveolar bone was greater and specific compared with other tissues. Furthermore, on day 7, ARG data revealed that 45 Ca on the control side was primarily localized to the periodontal ligament (PDL) space and alveolar bone crest and barely detected in the gingival tissues and deeper parts of the alveolar bone. On the ligature side, 45 Ca disappeared from the PDL and alveolar crest, but instead was broadly and significantly increased within the deeper zones of the alveolar bone and furcation areas and distant from the site of ligature placement and periodontal inflammation. In the shallow zone of the alveolar bone, these changes in 45 Ca levels on day 7 were consistent with decreases in the bone structural parameters (BV/TV and BMD), enhanced osteoclast presence, and suppressed levels of BAP expression in osteoblasts. In contrast, the deep zone and furcation area showed that TRAP-positive cells increased, but BAP expression was maintained in the resorption lacunae of the alveolar bone. CONCLUSION During periodontitis progression in rats, 45 Ca levels in the alveolar bone exhibited biphasic alterations, namely decreases and increases. These data indicate that periodontitis induces a wide range of site-specific Ca metabolism alterations within the alveolar bone.
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Affiliation(s)
- Ryutaro Kuraji
- Department of Life Science Dentistry, The Nippon Dental University, Tokyo, Japan.,Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan.,Department of Orofacial Sciences, University of California San Francisco, School of Dentistry, San Francisco, CA, USA
| | - Ya-Hsin Wu
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan.,Department of Periodontology, China Medical University Hospital, Taichung City, Taiwan
| | | | - Yukihiro Miyashita
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Saki Mishiro
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Hiroshi Ito
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Pachiyappan Kamarajan
- Department of Orofacial Sciences, University of California San Francisco, School of Dentistry, San Francisco, CA, USA
| | - Yvonne Kapila
- Department of Orofacial Sciences, University of California San Francisco, School of Dentistry, San Francisco, CA, USA
| | - Yukihiro Numabe
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
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16
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Kuraji R, Wu YH, Hashimoto S, Mishiro S, Maeda Y, Miyashita Y, Ito H, Miwa Y, Sunohara M, Kapila Y, Numabe Y. Temporal and dynamic changes in gingival blood flow during progression of ligature-induced periodontitis. Oral Dis 2020; 26:1292-1301. [PMID: 32153097 DOI: 10.1111/odi.13328] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Revised: 02/13/2020] [Accepted: 03/04/2020] [Indexed: 12/16/2022]
Abstract
OBJECTIVES To evaluate temporal changes in gingival blood flow (GBF) during progression of periodontitis in rats using a laser Doppler flowmeter (LDF) approach and to characterize morphological and biochemical features in the periodontium associated with GBF. MATERIALS AND METHODS Forty-two Wistar rats were divided into a ligature-induced periodontitis group and a control group. To induce periodontitis, ligatures were tied around maxillary first molars bilaterally. GBF was measured in palatal gingiva at pretreatment and following ligature placement after 30 min, 1, 3, 7, 14, 21, and 28 days using LDF with a non-contact probe. Bone loss and gene expression in gingival tissues were assessed using micro-computed tomography (μCT) and quantitative polymerase chain reaction (PCR), respectively. Immunostaining for vascular endothelial growth factor (VEGF) in the maxilla was also histologically evaluated. RESULTS GBF in the ligature group increased significantly compared with the control group 30 min after ligation. However, on days 3 and 7, GBF decreased in the ligature group. Also, after day 10, there was no difference in GBF between groups. The levels of alveolar bone loss, gene expression (interleukin-6, cluster of differentiation-31, VEGF-A, and lymphatic vessel endothelial hyaluronan receptor-1), and immunostained VEGF-positive vessels correlated well with changes in GBF. CONCLUSION PROGRESSION OF PERIODONTITIS: In rats was associated with a triphasic pattern of GBF, consisting of a short initial increase, followed by a rapid decrease, and then a gradual plateau phase.
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Affiliation(s)
- Ryutaro Kuraji
- Department of Life Science Dentistry, The Nippon Dental University, Tokyo, Japan
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
- Department of Orofacial Sciences, School of Dentistry, University of California San Francisco, San Francisco, CA, USA
| | - Ya-Hsin Wu
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
- Department of periodontology, China medical University Hospital, Taichung City, Taiwan
| | | | - Saki Mishiro
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Yuuki Maeda
- Department of General Dentistry, The Nippon Dental University Hospital, Tokyo, Japan
| | - Yukihiro Miyashita
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Hiroshi Ito
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Yoko Miwa
- Department of Anatomy, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Masataka Sunohara
- Department of Anatomy, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Yvonne Kapila
- Department of Orofacial Sciences, School of Dentistry, University of California San Francisco, San Francisco, CA, USA
| | - Yukihiro Numabe
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
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17
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Analyzing the Association between Hyperuricemia and Periodontitis: A Cross-Sectional Study Using KoGES HEXA Data. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17134777. [PMID: 32630802 PMCID: PMC7370102 DOI: 10.3390/ijerph17134777] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 06/18/2020] [Accepted: 06/27/2020] [Indexed: 01/05/2023]
Abstract
Hyperuricemia arises from the buildup of excessive uric acid in the blood, and it is implicated in the development of periodontitis. The objective of this study was to investigate the association between hyperuricemia and periodontitis using a cross-sectional study design and Korean Genome and Epidemiology Study Health Examinee (KoGES HEXA) data. This prospective cohort study used epidemiological data from the KoGES from 2004 to 2016. Among 173,209 participants, 8809 with hyperuricemia and 126,465 controls (non-hyperuricemia) were selected. This study defined hyperuricemia as >7.0 mg/dL of uric acid in men and >6.0 mg/dL in women. This study analyzed the history of periodontitis among hyperuricemia and control participants. Participants’ age, gender, income, obesity, smoking, alcohol consumption, and nutritional intake were all examined. Chi-square tests, independent t-tests, and two-tailed analyses were used for statistical analysis. The adjusted OR (aOR) of hyperuricemia for periodontitis was 0.89 (95% confidence interval (CI) = 0.81–0.96, p = 0.005). This study demonstrated that hyperuricemia was associated with periodontitis. This finding meant that elevated uric acid levels could have a positive effect on periodontitis. However, further studies should be performed to determine the range of uric acid levels beneficial to periodontal health.
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18
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Kamata Y, Kessoku T, Shimizu T, Kobayashi T, Kurihashi T, Sato S, Kuraji S, Aoyama N, Iwasaki T, Takashiba S, Hamada N, Kodama T, Tamura T, Ino S, Higurashi T, Taguri M, Yamanaka T, Yoneda M, Usuda H, Wada K, Nakajima A, Minabe M. Efficacy and safety of PERIOdontal treatment versus usual care for Nonalcoholic liver disease: protocol of the PERION multicenter, two-arm, open-label, randomized trial. Trials 2020; 21:291. [PMID: 32293522 PMCID: PMC7092586 DOI: 10.1186/s13063-020-4201-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Accepted: 02/24/2020] [Indexed: 12/11/2022] Open
Abstract
Background We report the first protocol for a multicenter, randomized comparison study to compare the efficacies of periodontal scaling and root-planing treatment against that of tooth-brushing treatment for nonalcoholic fatty liver disease (NAFLD) (PERION: PERIOdontal treatment for NAFLD). Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD, which can progress to cirrhosis and hepatocellular carcinoma. Increased endotoxemia is associated with the progression of NAFLD. Periodontal bacteria possess endotoxins; Porphyromonas gingivalis is well-known as a major pathogenic bacterium in periodontitis, and serum antibody levels for P. gingivalis are high in patients with periodontitis. Several reports have indicated that P. gingivalis is related to NAFLD. This study aims to investigate the effect of periodontal treatment for liver damage, P. gingivalis infection, and endotoxemia on patients with NAFLD. Methods We will include adult patients (20–85 years old) with NAFLD, alanine aminotransferase (ALT) ≥ 40 IU/L, and equivalent steatosis grade ≥ 1 (target sample size, n = 40 patients; planned number of patients with outcome data, n = 32). Participants will be randomly assigned to one of two groups: a scaling and root-planing group or tooth-brushing as the usual group. The primary outcome will be the change in ALT levels from baseline to 12 weeks; the key secondary outcome will be the change in the serum immunoglobulin G (IgG) antibody titer for P. gingivalis at 12 weeks. Discussion This study should determine whether periodontal treatment decreases liver damage, P. gingivalis infection, and endotoxemia in patients with NAFLD. Trial registration University Hospital Medical Information Network (UMIN) Clinical Trials Registry, ID: UMIN000022079.
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Affiliation(s)
- Yohei Kamata
- Department of Highly Advanced Oral Stomatology, Yokohama Clinic, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa, Yokohama, Kanagawa, 221-0835, Japan
| | - Takaomi Kessoku
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Tomoko Shimizu
- Department of Highly Advanced Oral Stomatology, Yokohama Clinic, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa, Yokohama, Kanagawa, 221-0835, Japan
| | - Takashi Kobayashi
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Takeo Kurihashi
- Department of Internal Medicine, Yokohama Clinic, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa, Yokohama, Kanagawa, 221-0835, Japan
| | - Satsuki Sato
- Department of Highly Advanced Oral Stomatology, Yokohama Clinic, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa, Yokohama, Kanagawa, 221-0835, Japan
| | - Syotaro Kuraji
- Department of Highly Advanced Oral Stomatology, Yokohama Clinic, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa, Yokohama, Kanagawa, 221-0835, Japan
| | - Norio Aoyama
- Division of Periodontology, Department of Oral Interdisciplinary Medicine, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan
| | - Tomoyuki Iwasaki
- Iwasaki Internal Medicine Clinic, 1-1-5 Furu-ruyokohama1F, Kamihoshikawa, Hodogaya-ku Yokohama, Kanagawa, 240-0042, Japan
| | - Shogo Takashiba
- Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan
| | - Nobushiro Hamada
- Division of Microbiology, Department of Oral Science Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan
| | - Toshiro Kodama
- Department of Implantology and Periodontology, Graduate School of Dentistry, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa, Yokohama, Kanagawa, 221-0835, Japan
| | - Toshiyuki Tamura
- Department of Highly Advanced Oral Stomatology, Yokohama Clinic, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa, Yokohama, Kanagawa, 221-0835, Japan
| | - Satoshi Ino
- Division of Prosthetic Dentistry, Department of Highly Advanced Stomatology, Graduate School of Dentistry, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa, Yokohama, Kanagawa, 221-0835, Japan
| | - Takuma Higurashi
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Masataka Taguri
- Department of Biostatistics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Takeharu Yamanaka
- Department of Biostatistics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Haruki Usuda
- Department of Pharmacology, Shimane University School of Medicine, 89-1 Enya-cho Izumo, Shimane, 693-0581, Japan
| | - Koichiro Wada
- Department of Pharmacology, Shimane University School of Medicine, 89-1 Enya-cho Izumo, Shimane, 693-0581, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Masato Minabe
- Division of Periodontology, Department of Oral Interdisciplinary Medicine, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan.
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Chen ZY, Ye LW, Zhao L, Liang ZJ, Yu T, Gao J. Hyperuricemia as a potential plausible risk factor for periodontitis. Med Hypotheses 2020; 137:109591. [PMID: 32007821 DOI: 10.1016/j.mehy.2020.109591] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2019] [Revised: 01/11/2020] [Accepted: 01/21/2020] [Indexed: 12/22/2022]
Abstract
Elevated blood uric acid (UA) levels have been positively associated with the severity of periodontitis. It thus brings out a hypothesis that hyperuricemia, a pathological elevation of blood UA, might be a risk factor for periodontitis. Namely, periodontitis individuals with Hu might acquire more severe periodontal destruction compared to those without Hu. To support the hypothesis, four aspects of evidences are proposed. First, hyperuricemia and periodontitis share many metabolic and inflammatory comorbidities such as metabolic syndrome, diabetes and cardiovascular diseases which are commonly related to elevated UA levels and gout. Second, observational and interventional studies have found altered UA levels in blood and saliva in periodontitis patients or after periodontal treatment, suggesting an epidemiological connection between hyperuricemia and periodontitis. Third, plausible immuno-metabolic mechanisms by which hyperuricemia might promote the progression of periodontitis are suggested, such as impaired immune response, oxidative stress, pathological bone remodeling and dysbiosis. The last, our empirical data exhibited elevated UA levels in gingival tissue in periodontitis mice compared to controls. If the hypothesis is true, given the high prevalence of the two conditions, hyperuricemia would be a significant risk factor increasing the global burden of periodontal diseases. Evidences on a directional correlation between hyperuricemia and periodontitis are sparse. Longitudinal and experimental studies would be necessary to determine the magnitude of periodontal risk, if any, exacerbated by hyperuricemia and the underlying mechanisms.
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Affiliation(s)
- Zi-Yun Chen
- Department of Periodontology, Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou, China
| | - Lu-Wen Ye
- Department of Periodontology, Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou, China
| | - Li Zhao
- Department of Prosthodontics, Guanghua School of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China
| | - Zhao-Jia Liang
- Department of Periodontology, Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou, China
| | - Ting Yu
- Department of Periodontology, Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou, China.
| | - Jie Gao
- Department of Periodontology, Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou, China
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The expression of macrophage migration inhibitory factor and intercellular adhesion molecule-1 in rats with periodontitis and atherosclerosis. Arch Oral Biol 2019; 107:104513. [DOI: 10.1016/j.archoralbio.2019.104513] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Revised: 07/30/2019] [Accepted: 07/30/2019] [Indexed: 12/11/2022]
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21
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Kuraji R, Hashimoto S, Ito H, Sunada K, Numabe Y. Development and use of a mouth gag for oral experiments in rats. Arch Oral Biol 2019; 98:68-74. [DOI: 10.1016/j.archoralbio.2018.11.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 10/18/2018] [Accepted: 11/10/2018] [Indexed: 12/12/2022]
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22
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Wu Y, Kuraji R, Taya Y, Ito H, Numabe Y. Effects of theaflavins on tissue inflammation and bone resorption on experimental periodontitis in rats. J Periodontal Res 2018; 53:1009-1019. [PMID: 30159985 PMCID: PMC6221153 DOI: 10.1111/jre.12600] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Revised: 06/29/2018] [Accepted: 07/23/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND OBJECTIVE Theaflavins (TFs), the major polyphenol in black tea, have the ability to reduce inflammation and bone resorption. The aim of this study was to evaluate the effects of TFs on experimental periodontitis in rats. MATERIAL AND METHODS Thirty rats were divided into five groups: Control (glycerol application without ligation), Ligature (glycerol application with ligation), TF1 (1 mg/mL TF application with ligation), TF10 (10 mg/mL TF application with ligation), and TF100 (100 mg/mL TF application with ligation). To induce experimental periodontitis, ligatures were placed around maxillary first molars bilaterally. After ligature placement, 100 μL glycerol or TFs were topically applied to the rats daily, and rats were euthanized 7 days after ligature placement. Micro-computed tomography was used to measure bone resorption in the left side of the maxilla, and quantitative polymerase chain reaction was used to measure the expression of interleukin (IL)-6, growth-regulated gene product/cytokine-induced neutrophil chemoattractant (Gro/Cinc-1, rat equivalent of IL-8), matrix metalloproteinase-9 (Mmp-9), receptor activator of nuclear factor-kappa Β ligand (Rankl), osteoprotegerin (Opg), and the Rankl/Opg ratio in gingival tissue. With tissue from the right side of the maxilla, hematoxylin and eosin staining was used for histological analysis, immunohistochemical staining for leukocyte common antigen (CD45) was used to assess inflammation, and tartrate-resistant acid phosphatase (TRAP) staining was used to observe the number of osteoclasts. RESULTS The TF10 and TF100 groups, but not the TF1 group, had significant inhibition of alveolar bone loss, reduction in inflammatory cell infiltration in the periodontium, and significantly reduced numbers of CD45-positive cells and TRAP-positive osteoclasts compared with the Ligature group. Correspondingly, the TF10 and TF100 groups had significantly downregulated gene expression of IL-6, Gro/Cinc-1(IL-8), Mmp-9, and Rankl, but not of Opg. Consequently, Rankl/Opg expression was significantly increased in the Ligation group but was attenuated in the TF10 and TF100 groups. CONCLUSION The results of this study suggest that topical application of TFs may reduce inflammation and bone resorption in experimental periodontitis. Therefore, TFs have therapeutic potential in the treatment of periodontal disease.
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Affiliation(s)
- Ya‐Hsin Wu
- Department of PeriodontologyThe Nippon Dental University School of Life Dentistry at TokyoTokyoJapan
| | - Ryutaro Kuraji
- Department of PeriodontologyThe Nippon Dental University School of Life Dentistry at TokyoTokyoJapan
- Department of Life Science DentistryThe Nippon Dental UniversityTokyoJapan
| | - Yuji Taya
- Department of PathologyThe Nippon Dental University School of Life Dentistry at TokyoTokyoJapan
| | - Hiroshi Ito
- Department of PeriodontologyThe Nippon Dental University School of Life Dentistry at TokyoTokyoJapan
| | - Yukihiro Numabe
- Department of PeriodontologyThe Nippon Dental University School of Life Dentistry at TokyoTokyoJapan
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23
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Fujita M, Kuraji R, Ito H, Hashimoto S, Toen T, Fukada T, Numabe Y. Histological effects and pharmacokinetics of lipopolysaccharide derived from Porphyromonas gingivalis on rat maxilla and liver concerning with progression into non-alcoholic steatohepatitis. J Periodontol 2018; 89:1101-1111. [PMID: 29799627 DOI: 10.1002/jper.17-0678] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Revised: 04/10/2018] [Accepted: 04/29/2018] [Indexed: 11/10/2022]
Abstract
BACKGROUND Non-alcoholic steatohepatitis (NASH) is one of the chronic liver diseases that can develop into hepatocirrhosis. The purpose of the present study was to investigate the impact of lipopolysaccharide (LPS) from Porphyromonas gingivalis (P. gingivalis) on NASH onset, and to determine the biodistribution of double-radiolabeled LPS (R-LPS) biosynthesized in P. gingivalis. METHODS Rats fed a basal diet (BD) or a high-fat diet (HD) were injected with P. gingivalis-LPS or R-LPS into the palatine gingiva around the right maxillary first molar, and were classified into the following 4 groups: BD/LPS (-), BD/LPS (+), HD/LPS (-), and HD/LPS (+) or 2 groups: BD/R-LPS and HD/R-LPS. RESULTS Inflammation in the gingiva of the LPS (+) groups progressed significantly more than the LPS (-) groups. Furthermore, in the HD/LPS (+) liver, histologic analysis confirmed the presence of NASH, characterized by large fat droplets, ballooning degeneration, and infiltration of inflammatory cells. When 3 H, 14 C-R-LPS was injected into the palatine gingiva, radioactivity in the right palatal mucosa of HD/R-LPS rats was the highest in comparison with other regions and was significantly elevated after 24 hours compared to BD/R-LPS rats. Autoradiographic analysis of the maxilla showed distributions from the palatal mucosa to the hard palate and the interdental region. Radioactivity in organs of both BD/R-LPS and HD/R-LPS rats were mostly localized to the liver even after 24 hours. CONCLUSION The present study suggests that the transfer of P. gingivalis-LPS from the oral cavity to the liver plays an important role in disease exacerbation of NASH.
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Affiliation(s)
- Miyako Fujita
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Ryutaro Kuraji
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan.,Department of Life Science Dentistry, The Nippon Dental University, Tokyo, Japan
| | - Hiroshi Ito
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | | | - Toshiyuki Toen
- Dental Research Institute, Radio Isotope Center, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Tetsuya Fukada
- Dental Research Institute, Radio Isotope Center, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Yukihiro Numabe
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
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Damanaki A, Nokhbehsaim M, Hiththetiya K, Memmert S, Gao J, Nguyen KA, Götz W, Jäger A, Wahl G, Deschner J. Characterization of a diet-induced obesity rat model for periodontal research. Clin Oral Investig 2018; 23:937-946. [PMID: 29907930 DOI: 10.1007/s00784-018-2514-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Accepted: 06/04/2018] [Indexed: 11/26/2022]
Abstract
OBJECTIVES Obesity is associated with periodontitis, but the mechanisms underlying this association have yet to be unraveled. The present investigation was to evaluate a common rat model, in which obesity is induced by high-fat, high-sucrose diet (HFSD), for its applicability in periodontal research. MATERIALS AND METHODS Ten male Wistar rats were fed a 3-month HFSD along with a matching control group. Afterwards, the body weight, adipocyte morphology, leptin and adiponectin levels in adipose tissue, gingiva, and serum as well as the serum levels of triglyceride, cholesterol, and glucose were analyzed. For statistical analyses, parametric and non-parametric tests were applied (p < 0.05). RESULTS Body weight was significantly higher in the HFSD group after dieting as compared to control. HFSD caused a significant increase in serum triglyceride, low-density lipoprotein cholesterol, and leptin levels and a significant decrease in high-density lipoprotein cholesterol. Furthermore, adipose tissue from HFSD rats exhibited significantly larger adipocytes, displayed a significant upregulation of leptin and, surprisingly, elevated adiponectin levels, which is in contrast to chronic obesity in humans. Although leptin and adiponectin were also observed in gingival biopsies, no obvious differences between the groups were found. CONCLUSIONS Although this rat diet-induced obesity model is characterized by changes typical of obesity, it also has limitations, which have to be considered when data, especially with regard to adipokines, are extrapolated to humans. CLINICAL RELEVANCE The rodent diet-induced obesity model may be useful for unraveling pathomechanisms underlying the association between obesity and periodontal destruction but conclusions have to be drawn with caution.
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Affiliation(s)
- Anna Damanaki
- Section of Experimental Dento-Maxillo-Facial Medicine, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Welschnonnenstrasse 17, 53111, Bonn, Germany
| | - Marjan Nokhbehsaim
- Section of Experimental Dento-Maxillo-Facial Medicine, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Welschnonnenstrasse 17, 53111, Bonn, Germany
| | | | - Svenja Memmert
- Section of Experimental Dento-Maxillo-Facial Medicine, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Welschnonnenstrasse 17, 53111, Bonn, Germany
- Department of Orthodontics, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany
| | - Jinlong Gao
- Westmead Institute for Medical Research and Faculty of Dentistry, University of Sydney, Sydney, Australia
| | - Ky-Anh Nguyen
- Westmead Institute for Medical Research and Faculty of Dentistry, University of Sydney, Sydney, Australia
| | - Werner Götz
- Department of Orthodontics, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany
| | - Andreas Jäger
- Department of Orthodontics, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany
| | - Gerhard Wahl
- Department of Oral Surgery, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany
| | - James Deschner
- Section of Experimental Dento-Maxillo-Facial Medicine, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Welschnonnenstrasse 17, 53111, Bonn, Germany.
- Noel Martin Visiting Chair, Faculty of Dentistry, University of Sydney, Sydney, Australia.
- Department of Periodontology and Operative Dentistry, University Medical Center, Johannes Gutenberg University, Augustusplatz 2, 55131, Mainz, Australia.
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