Ulvi Kahraman Gürsoy
Associate professor. Department of Periodontology, Institute of Dentistry, University of Turku, Turku, Finland
Georgios Belibasakis
Professor. Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden
Daniel Belstrøm
Associate professor. Section for Clinical Oral Microbiology, Periodontology, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark
Timo Sorsa
Professor. Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden and Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Anne Isine Bolstad
Professor. Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Bergen, Norway
Headlines
Periodontitis is a well-orchestrated disease of the tooth supporting tissues, in which the pathogens, pathogen-associated molecular patterns, and host-response play significant roles
Molecular markers of infection and host-response, and related biological-pathways can be used to diagnose periodontitis and also can be considered as actionable therapeutic targets
Periodontitis is a chronic inflammatory disease of tooth-supporting tissues characterized by the breakdown of periodontal attachment and alveolar bone. The onset age and the progression rate of the disease vary depending on the presence of inherited and acquired risk factors and oral hygiene measures. The relatively slow-progressing forms of periodontitis are usually diagnosed in the third to fourth decades of life, while aggressive forms of the disease can be detected in young adults. Periodontitis proceeds in an asymptomatic pattern, meaning that initial stages of the disease are relatively underdiagnosed. Today, with the improvements in technology, it is possible to detect sub-clinical changes in the periodontal tissues by measuring the levels of non-invasively collected host- or bacteria-originated proteins, i.e. periodontal biomarkers. The present narrative review aims to present the current evidence of the clinical use of infection- and inflammation-related proteins as biomarkers. The molecular markers that can be targeted in periodontal disease treatment will also be discussed.
Molecular signatures of periodontitis: From diagnosis to disease modification
Periodontitis is the inflammatory disease of tooth-supporting tissues. It has a microbial etiology and a chronic degradative character. Periodontitis is accepted as a multifactorial disease, meaning that the severity and extent of observed periodontal tissue degradation can be modified by several systemic and local risk factors [1].
While the pathogenesis of periodontitis shows similarities among the population, the initiation, progression, and remission of the disease show individual and site-specific variations. In addition, progression of periodontitis demonstrates a non-linear chaotic dynamical process [2]. Indeed, the phrase once a periodontitis, always a periodontitis indicates that even after successful treatment, patient will be under the increased risk of recurrent periodontitis and requires lifelong maintenance therapy [3]. Routine dental check-ups are strongly advised to detect periodontitis at its very early stages and inhibit its progression before an irreversible tissue damage occurs. However, full-mouth periodontal screening of large populations might be costly and time taking. To overcome that obstacle, one approach is to categorize the population based on its periodontal risk status [4][5]. With that, it can be possible to personalize the preventive care and treatment measures by 1) monitoring the individuals at high-risk groups more often to diagnose periodontitis at its very early stages, 2) to apply adjuvant therapies to periodontitis patients with weakened host-response, and 3) to inhibit the risk of relapse after periodontal treatment, especially in susceptible patients. Unfortunately, such aims are not always achievable, as national oral health care systems do not necessarily cover frequent dental check-ups or adjuvant therapy applications, which bring significant cost to the patient over time.
Technological improvements over the past three-four decades enabled us to understand the periodontitis pathogenesis more than before. Increased sensitivities in biomarker detection methods and decreased methodological costs allowed researchers to study various bacteria- or host-originated proteins as diagnostic markers of disease or actionable therapeutic targets for treatment (Figure 1).
With the aid of the rapid developments in nano- and microfluid technologies, various point-of-care/lab-on-a-chip tests and paper-based/flow-cytometry based platforms were developed to be used in dental clinics [6]. In this review, aim will be to answer the following questions; 1) What is the role of diagnostic markers of periodontitis? 2) How can such markers add information to clinical diagnosis? 3) How can products aiming at modulating inflammation be used as an adjunctive tool to mechanical infection control procedures in periodontal therapy?
Diagnostic markers of periodontitis
Periodontitis is diagnosed and evaluated based on clinical and radiographic measurements, such as probing pocket depth (PPD), clinical attachment level (CAL) and bleeding on probing (BOP). It has been this way for more than 50 years and is still the case with the newest classification of periodontitis, where clinical and radiographic measurements continue to be the main determinants, used for staging and grading of periodontitis [7]. The main caveat of using PPD, CAL and radiographic bone loss alone is that they can only be used to identify periodontitis, when irreversible tissue damage has occurred. This is why diagnostic methods capable of identification of periodontitis at preclinical stages are urgently needed.
Periodontitis is a multifactorial disease and the subgingival microbiota and the host immune system are the main acts in the pathogenesis of periodontitis [8]. The first insight on the role of the oral microbiota in periodontal disease development was based on culture based microbial techniques. The development of culture ind
