Periodontal Medicine Research Articles

Relationship of COVID-19 pathogenesis for periodontal medicine research. Part I: Pathogenesis of COVID-19

Cell invasion mediated by angiotensin-converting enzyme 2 (ACE2) ectoenzyme and cellular proteases, such as trypsin-like proteases, cathepsins, transmembrane serine protease 2 and furin, target different tissues and organs as lung, gut, colon, ileum, kidney, gallbladder, heart muscle, epididymis, breast, ovary, stomach, bile duct, liver, oral cavity, lung, thyroid, esophagus, bladder, breast, uterus, prostate, pancreas, cerebellum, as well as calyx secreting cells in the nasal and sinus tissue. Loss of homeostasis of the renin-angiotensin system deregulates different axes compromising metabolic, cardiorespiratory, renal and hepatic control. SARS-CoV-2 infected cell undergoes pyroptosis and releases molecular patterns associated with damage: pro-inflammatory interleukin (IL) -1b, IL-6, IL-8, IL-10, IL-17, induced protein-10, interferon gamma, interferon gamma-induced protein-10, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, macrophage inflammatory protein 1α and 1β, monocyte chemotherapy activating protein 1, inflammatory macrophage protein 1a, tumor necrosis-α, and mediators of immune-mediated inflammatory diseases. Cytokine storm and non-neutralizing antibodies produced by B cells circulate, cause/exacerbate damage to various organs. During viral replication and low oxygen saturation, loss of HIF-mediated cell homeostasis can lead to cell death/lysis and tissue damage, related to the hyperinflammatory response. The SARS-CoV-2-ACE2 can increase permeability, inflammation and microbial transmission by bacteremia or endotoxemia, in addition to dysbiosis. Thrombotic potential and the immunoinflammatory imbalance compromise function or lead to injuries and multiple organ failure. Infection by SARS-CoV-2 has the potential to modify the natural history of diseases, the relationships or interactions between the different systems and pathologies and the effects of their treatments, as in periodontal medicine approach.

Relationship of COVID-19 pathogenesis for periodontal medicine research. Part II: Periodontal Medicine

The dysfunctional immunoinflammatory response to SARS-CoV-2 infection leads to excessive infiltration of monocytes, macrophages and T cells, non-neutralizing antibody, systemic cytokine storm, microthrombi mediated by tissue factor and oxidative stress, lower platelet counts, increased D-dimer, C-reactive protein and coagulation abnormalities, increased vascular permeability, pulmonary edema and pneumonia, and widespread inflammation and multi-organ damage. Periodontal diseases have a chronic and multifactorial inflammatory profile, of infectious origin, with bidirectional systemic interactions linked to over 50 systemic conditions/diseases. Immunoinflammatory response of periodontal tissues to the microbial challenge, protective/repair response and the local destruction of periodontium influence and are influenced by systemic conditions/diseases. Renin-angiotensin system/ACE inhibitors are also related to pathogenesis of COVID-19 by SARS-CoV-2-ACE2 and to pathogenesis of periodontitis, through bone resorption regulated by the ACE2/Ang-(1-7)/MasR axis and IL1-b, positive regulation of the kinin/receptor pathway B2 due to Toll-like receptor 2 inflammation and Th1/Th17 responses, the expression of the type 1 angiotensin II receptor in the inflamed gingival tissue, and modulating IL-1β-induced IL-6 production in human gingival fibroblasts. It is possible that SARS-CoV-2 infection increases local inflammatory events in periodontal tissue leading to destruction of periodontal tissues, probably enhanced by the systemic effects of periodontitis. Despite limited or non-existent scientific evidence on the effects of COVID-19 on periodontal diseases and their systemic interactions to date, it is possible to expect its impact on periodontal medicine research from the natural history of periodontal diseases to their pathogenesis and relationship with systemic conditions and response to treatment, as an environmental and acquired risk factor.

What is the future of Periodontal Medicine?

In the last five decades, considerable progress has been made towards understanding the etiology and pathogenesis of periodontal diseases and their interactions with the host. The impact of an individual periodontal condition on systemic homeostasis became more evident because of this knowledge and prompted advances in studies that associate periodontitis with systemic diseases and conditions. The term Periodontal Medicine describes how periodontal infection/inflammation can affect extraoral health. This review presents the current scientific evidence on the most investigated associations between periodontitis and systemic diseases and conditions, such as cardiovascular diseases, diabetes, preterm birth and low birth weight, and pneumonia. Additionally, other associations between periodontitis and chronic inflammatory bowel disease, colorectal cancer, and Alzheimer's disease that were recently published and are still poorly studied were described. Thus, the aim of this review was to answer the following question: What is the future of Periodontal Medicine? Epidemiological evidence and the evidence of biological plausibility between periodontitis and general health reinforce the rationale that the study of Periodontal Medicine should continue to advance, along with improvements in the epidemiological method, highlighting the statistical power of the studies, the method for data analysis, the case definition of periodontitis, and the type of periodontal therapy to be applied in intervention studies.

Periodontal disease and cancer: Periodontal medicine in the multi-omics era

Periodontal disease and cancer: Periodontal medicine in the multi-omics era

The Ubiquitin Proteasome System in Periodontal Disease: A Comprehensive Review

The turnover of intracellular proteins is a highly selective and regulated process. This process is responsible for avoiding injury and irreparable breakdown of cellular constituents. Its impairment disrupts cellular stability, integrity, and homeostasis. The ubiquitin-proteasome system (UPS) is responsible for this programmed degradation of most intracellular proteins. This process involves a cascade of enzymes that involves the ubiquitin conjugation to a target substrate protein, its recognition and degradation by the proteasome. The turn-over of intracellular proteins is a non-stop ubiquitous process that regulates a series of mechanisms, for instance transcription, translation, endocytosis. In addition, proteasome act by releasing peptides that may serve to other purposes, such as antigen presentation in immune actions and enzymatic flagging toward biosynthesis and gluconeogenesis. The role of the UPS impairment in periodontal diseases is gaining growing. This acquaintance might contribute to the development of novel therapeutic applications. Thus, this review focuses on the latest progresses on the role of the UPS and its signaling pathways in Periodontal Medicine. Furthermore, we discuss the potential of UPS-based drugs development to be used in periodontal disease therapy.

Steven Offenbacher, DDS, PhD, MMSc: The gifts of a giant in science and the father of periodontal medicine.

Steven Offenbacher, DDS, PhD, MMSc: The gifts of a giant in science and the father of periodontal medicine.

Extracellular Vesicles in Periodontal Medicine : The Candidates Linking Oral Health to General Health

The term, periodontal medicine is used to describe the multitude of systemic diseases which are regarded to link periodontal disease. The concept of periodontal medicine has been widely accepted today, however, the molecular mechanisms which periodontal diseases impact general health in whole body are not elucidated in detail. Extracellular vesicles (EVs) and outer membrane vesicles (OMVs) are the nano-sized particles released from mammalian cells and bacterial cells resectively, which influence the health and various disease by transporting biological factors to the neighbor and distant cells. In this review, we will discuss whether EVs and OMVs produced in periodontal diseases could be implicated in periodontal medicine.

An Evidence-Based Update on the Molecular Mechanisms Underlying Periodontal Diseases.

Several investigators have reported about the intricate molecular mechanism underlying periodontal diseases (PD). Nevertheless, the role of specific genes, cells, or cellular mechanisms involved in the pathogenesis of periodontitis are still unclear. Although periodontitis is one of the most prevalent oral diseases globally, there are no pre-diagnostic markers or therapeutic targets available for such inflammatory lesions. A pivotal role is played by pro- and anti-inflammatory markers in modulating pathophysiological and physiological processes in repairing damaged tissues. In addition, effects on osteoimmunology is ever evolving due to the ongoing research in understanding the molecular mechanism lying beneath periodontal diseases. The aim of the current review is to deliver an evidence-based update on the molecular mechanism of periodontitis with a particular focus on recent developments. Reports regarding the molecular mechanism of these diseases have revealed unforeseen results indicative of the fact that significant advances have been made to the periodontal medicine over the past decade. There is integrated hypothesis-driven research going on. Although a wide picture of association of periodontal diseases with immune response has been further clarified with present ongoing research, small parts of the puzzle remain a mystery and require further investigations.

Awareness of Periodontal Medicine among Medical Students at a Tertiary Care Center

Introduction: Tissue destruction of supporting periodontal tissues is mediated by an overreactive immune inflammatory response to bacteria in the subgingival environment. Tissue destruction in periodontitis occurs by the stimulatory action of pro inflammatory cytokines and proteolytic enzymes released by neutrophils, macrophages, and the action of bone resorption mediators, all of which are being regulated by B and T cells. Periodontitis act as a focus of infection and bacteria metastases through blood stream to various vital organs like heart, lungs, joints and amniotic fluid.
 Objective: To assess the awareness of periodontal medicine among medical students at a tertiary care center in Kathmandu.
 Methods: A total of 115 subjects were taken for the present study. Data was collected using a questionnaire which included questions used to assess the knowledge about periodontal diseases and its possible effects on systemic conditions.
 Results: Out of the total participants, 58 (50.4%) said that periodontal disease was not related to coronary heart diseases. Only 14 (12.2%) had an idea about the association of pre-term birth and periodontitis. While 86 (74.8%) knew the impact of diabetes on periodontium, only 34 (29.6%) said that there was an association between periodontitis and hospital acquired pneumonia.
 Conclusion: Knowledge about the association of periodontal disease with various systemic conditions is not satisfactory among the various medical students of this hospital.

Awareness and practices of general practitioners towards the oral-systemic disease relationship: A regionwide survey in France.

GPs registered in the north of France were invited to complete an online self-administered questionnaire through local divisions of the French Medical Board. The questionnaire was divided into four sections: socio-demographic aspects, knowledge, practices, and an overview. The questionnaire was completed by 253 GPs. Among these, 75% were aware of the association between periodontitis (PD) and diabetes, and 53% to 59% were aware of the impact of PD on cardiovascular diseases, inflammatory bowel diseases, and respiratory infections. Few GPs identified PD as a possible risk factor of rheumatoid arthritis and Alzheimer disease (35.18% and <15%, respectively); 74.31% of GPs reported never asking their patients about their periodontal health. However, a personal history of PD and professional experiences seem to influence the medical practices of GPs to include oral examination. GPs largely self-rated their knowledge of the oral-systemic disease connection as being insufficient and were favourable to completing an up-to-date training course (86.56%). French GPs' knowledge about the association of PD with systemic diseases seems to be fair, but discrepancies in their daily clinical routine were found. Promisingly, a positive attitude was observed towards improving their knowledge of oral-systemic diseases link. These results indicate the importance to reinforce collaboration between medical doctors and oral health care specialists.

Periodontal Medicine: 100 Years of Progress

Periodontal medicine is a term used to describe how periodontal infection/inflammation may impact extraoral health. Periodontitis has been linked to over 50 systemic diseases and conditions. As part of the Journal of Dental Research’s Centennial Celebration, this narrative review discusses periodontal medicine research done over the past 100 y, with particular focus on the effects of periodontal disease on 3 pathological conditions: cardiovascular disease, diabetes mellitus, and adverse pregnancy outcomes. We selected 29 total studies that were the “first” of their kind, as they provided novel observations or contributed to shifting paradigms as well as important studies that made strong contributions to progress in understanding relationships to the systemic conditions. These studies were organized in an overview timeline and broken down into timelines by topic: cardiovascular disease (n = 10), diabetes (n = 12), and adverse pregnancy outcomes (n = 7). Overall, the majority of cross-sectional, case-control, and longitudinal studies have revealed positive associations between poor periodontal status and cardiovascular disease, diabetes metabolic control, and a number of adverse pregnancy outcomes, and these associations are upheld in systematic reviews. Findings from randomized controlled trials testing the effects of periodontal therapy on systemic health outcomes were conflicting and inconsistent. While there has been a great deal of progress, we highlight lessons learned and make comments and suggestions on a number of key aspects, including the heterogeneity of case definitions of periodontal disease across studies, accounting for features of the periodontal phenotype that are most relevant to the biological link between periodontitis and systemic outcomes, the role of other comorbid inflammatory conditions, selection of study participants, and timing and intensity of the periodontal intervention.

Knowledge and Opinion of Internists and Gynecologists Physicians on Periodontal Medicine.

To evaluate the knowledge, opinions, and behaviours of physicians in the field of internal medicine and gynecology regarding periodontal disease and its systemic implications. A questionnaire was distributed by hand and via e-mail to internists and gynecologists working in hospitals and community clinics. The questionnaires included items regarding personal and professional status, subject-related characteristics, dental history and knowledge in periodontal medicine. All completed questionnaires were reviewed and analysed according to discipline and personal experience. Statistical differences were tested using the chi-squared analysis. A total of 97 questionnaires were reviewed and included 56 internists and 41 gynecologists. The mean age was 39.7 years (range 29-82) and the percentage of females was 54%. Overall, general knowledge regarding periodontitis differed significantly between internists and gynecologists (80% vs 32% correct answers per group, respectively). Nearly 60% of responders (both internists and gynecologists) knew the correct cause of periodontal disease. Although half of the responders had personal experience in the field of periodontology, this experience was not noticeable regarding their knowledge in periodontal medicine. The majority of responders (58%) agreed that there is a need for more periodontal education in general medicine. The present study indicates a clear lack of knowledge of both internists and gynecologists regarding periodontitis and its systemic complications. Personal periodontal experience did not change the degree of familiarity with periodontal medicine.

Lifestyle and periodontitis: The emergence of personalized periodontics.

Personalized medicine is a medical model that involves the tailoring of healthcare - with medical decisions, practices, and/or products being customized to an individual patient. In this model, diagnostic testing is often employed for selecting appropriate and optimal therapies based on the context of a patient's genetic content or other epidemiologic, sociologic, molecular, physiologic, or cellular analyses. With the advent of major advances in periodontal medicine, including genomic discoveries and greater understanding of the multifactorial nature of periodontitis, it seems that the time is ripe to use personalized medicine as a model for personalized periodontics. This volume of Periodontology 2000 explores how new advances in our understanding of periodontitis within a medical model can evolve into new treatment strategies tailor-made for individual patients and not merely based on wholesale treatment paradigms.

The state of the art research findings on the relationship between chronic periodontitis and Alzheimer's disease: a review

Along with the development of periodontal medicine, there is a growing number of evidence showing that periodontitis could influence systemic health. Periodontitis is a chronic inflammatory disease caused by microbial infection mediated by dental plaque. Periodontal pathogenic microorganisms and its toxic products can disseminate through the blood stream or may cause the host immune response, which may lead to pathological changes of cerebral vessels and brain tissues to establish connection with Alzheimer's disease (AD). AD is a progressive neurodegenerative disease characterized by progressive memory loss, language and cognitive dysfunction. This article reviewed the association between chronic periodontitis and AD.

Serum interleukin-17 (IL-17) in chronic periodontitis patients

Introduction: Explorations into the periodontal medicine relationship have discovered interleukin-17 (IL-17) cytokine as one of the pro-inflammatory mediators that play a crucial role in the initiation and progression of the chronic periodontal disease. This case and control study aimed to compare the serum IL-17 concentration between chronic periodontitis and healthy subjects and to assess the relationship between the IL-17 serum and the clinical periodontal parameters in chronic periodontitis patients. Methods: This study was a case-control study. The subjects were selected using purposive sampling method. The periodontal screening assessment in the Family Treatment Center and Postgraduate Dental Clinic, Universiti Sains Malaysia Hospital. A total of 55 samples who fit with the inclusion and exclusion study criteria of full-mouth clinical periodontal records together with blood serums were obtained from 28 chronic periodontitis patients and from 27 healthy subjects. The concentration of IL-17 cytokine in serum was measured using ELISA test. Results: Subjects with periodontal disease presented significantly worse clinical parameters (p&lt;0.001) compared to control. The level of serum IL-17 concentration was significantly higher (p=0.026) in chronic periodontitis subjects 3.6 (1.03) pg/mL compared to the control 3.1 (0.70) pg/mL. Conclusions: There was no correlation between the level of IL-17 concentration in the serum and clinical periodontal parameters.

Periodontal inflamed surface area and periodontal case definition classification

Objective: To assess whether a higher periodontal inflamed surface area (PISA) may reflect more severe periodontitis, and if so, to calculate which cut-off point should be used to classify a patient as suffering from periodontitis.Material and methods: Eighty subjects were selected based on their periodontal status and were divided into 4 groups of 20 each; periodontally healthy, mild periodontitis, moderate periodontitis and severe periodontitis. In addition, demographic data, smoking status and socioeconomic status were also recorded.Results: The highest mean PISA value was obtained for the severe periodontitis group (2309.42 ± 587.69 mm2) and the least for the periodontally healthy (34.30 ± 16.48 mm2). The PISA values corresponding to the three categories of periodontitis severity were significantly higher than the periodontally healthy group. When receiver operating characteristic (ROC) analysis was performed, a PISA value ≥130.33 mm2 predicted the presence of periodontitis with a sensitivity of 98% and a specificity of 100%.Conclusions: PISA is a periodontal parameter that may be used in conjunction with the Centers for Disease Control and Prevention – American Academy of Periodontology case definition classification in periodontal medicine research.

Association between Periodontal Health Status and Cognitive Abilities. The Role of Cytokine Profile and Systemic Inflammation.

Background: Contemporary neurobiology, periodontal medicine, and immunology are now focusing on the relationship between chronic periodontitis and systemic diseases, which also include Alzheimer’s disease (AD). However a causative relationship between dementia and periodontitis has yet to be confirmed.Objective: The aim of the study was to determine whether periodontal health status and cognitive abilities are correlated with the relative changes in systemic measures of pro- and anti-inflammatory cytokines as a reflection of systemic inflammation. We hypothesized that poor periodontal health status may be associated with cognitive impairment and dementia via the exacerbation of systemic inflammation.Methods: Based on the periodontal and psychiatric examinations and the cytokine levels produced by unstimulated and LPS-stimulated PBL isolated from 128 participants, we have examined if the coexisting of these two clinically described conditions may have influence on the systemic inflammation. Mini-Mental State Examination (MMSE) and Bleeding on Probing (BoP) test results were combined into the one mathematical function U, which determines the severity of specific condition, called Cognitive and periodontal impairment state. Similarly, the levels of cytokines were combined into the one mathematical function V, whose value determines the level of Inflammatory state. The correlation between U and V was determined.Results: These results confirm that the presence of cognitive decline and the additional source of pro-inflammatory mediators, like periodontal health problems, aggravate the systemic inflammation.Conclusion: It is most likely that the comorbidity of these two disorders may deepen the cognitive impairment, and neurodegenerative lesions and advance to dementia and AD.

Evaluation of Liver Chemistry Tests and Clinical Parameters in Patients with Periodontal Disease and Chronic Hepatitis C

The concept of periodontal medicine has been created by taking into consideration the strong connection between the development of the periodontal disease and other general conditions. The presence in blood, saliva and gingival fluid of certain inflammatory markers that are common for the two conditions � periodontitis and chronic hepatitis C, that can generate the appearance of the periodontal inflammation, can be an explication for the probable interconnection of the two conditions. The purpose of this pilot study is to investigate whether chronic hepatitis C can be a worsening factor for the development of the periodontal disease, by setting correlations between the periodontal pathology and some metabolic markers of both hepatitis C and periodontitis patients in comparison to periodontitis-only ones. Positive correlations would justify the expansion of the study for a larger group of patients and the dosage of inflammatory markers for biologic fluids such as blood, saliva and gingival fluid.

Periodontal Diseases and Systemic Disorders: What Do Our Doctors Know? A General Practitioner's Survey Conducted in Southern France

ObjectivesWith 39,359 entries on PubMed, periodontal medicine has a prominent position in periodontal research. Good patient care requires well-advised physicians, and whereas the dental community is informed about the relationships between periodontal diseases (PDs) and an increasing number of systemic pathologies, we wondered whether general practitioners were too. Thus, we aimed to evaluate their knowledge of the links between periodontal and systemic diseases. MethodsTo this end, we sent an electronic questionnaire to the 2350 general practitioners registered to the URPS (Union régionale des Professionnels de Santé) of Midi-Pyrénées, France. They were asked about their practice, their attitude during a medical examination, and their knowledge about PDs. ResultsThe analysis of 222 properly answered questionnaires showed that while most general practitioners are aware of the relationships between PDs and diabetes or cardiovascular diseases, the majority of them are unaware that obesity and respiratory and joint diseases are also concerned. Indeed, 94% of the questioned subjects consider their insight of PDs to be insufficient. Nevertheless, more than half of the interrogated physicians cared about their patients' oral health and dental care. ConclusionsEducation regarding relationships between periodontal and systemic diseases must be improved among general practitioners who are in the front line to refer high-risk patients to a periodontist.

Periodontal Medicine—New Diagnostic Opportunities

Purpose of Review We examined the literature on periodontal medicine to determine how this field has influenced the diagnosis of periodontal diseases and the search for biomarkers in oral fluids.