Periodontal Disease‘Omic technologies in periodontitis research

Background.—Within the field of periodontology,research into biomarkers has been ongoing for sometime. Developments in such technologies as genomics,transcriptomics, proteomics, and metabolomics (‘omictechnologies) may help to analyze the information onperiodontitis relative to the many cell types, cell products,and interactions that make this a complex disease entity.The recent advances in human periodontal researchinvolving the ‘omic technologies were documented.

Methods.—Articles were sought through the Medlinedatabase that detailed various ‘omic technologies withrespect to periodontal research. A total of 161 articleswere identified that reported various biomarker and‘omic research efforts (Fig 2). These were analyzed fortheir contributions to a better understanding of peri-odontal disease.

Results.—The ‘omic technologies that were analyzedincluded genomics, transcriptomics, proteomics, metabo-lomics, and systems biology. Each was described alongwith its findings with respect to periodontal disease.

Genomics is the study of whole genomes. Genome-driven individualized medicine, in which changes tomultiple genes are taken into account for the diagnosisand treatment of conditions, is already being used. Changes

Fig 2.—The compartments available for studying periodontal dis-ease using ‘omic technologies. (Courtesy of Grant MM: What do‘omic technologies have to offer periodontal clinical practice inthe future? J Periodont Res 47:2-14, 2012.)

in individual genes (gene polymorphism) have been evalu-ated with respect to disease risk, severity, and therapeuticoutcome for several diseases. Gene polymorphisms areprevalent, with the most common type being the singlenucleotide polymorphism (SNP), which affects an individ-ual base pair. SNP research relevant to periodontal diseasehas focused on cytokines, but also involved some work onhuman leukocyte antigens, immunoreceptors, proteases,structural molecules, and other proteins. The researchhas narrowed the scope to studies of six genes: interleukin1 (IL1), tumor necrosis factor a (TNFa), Fcg receptors, ma-trix metalloproteinases (MMPs), cathepsin C, and vitamin Dreceptor. Although IL1 SNPs may be more associated withenvironmental influences, Fcg receptor polymorphismstend to be associated with aggressive, chronic forms of peri-odontitis. The genetic basis for periodontitis accounts forabout half of the population variance in chronic peri-odontal disease. One potential SNP was significantly associ-ated with aggressive periodontitis: GLT6D1, which encodesfor a glycosyltransferase 6 family protein. It was highly ex-pressed in the gingival connective tissues and may alter im-mune response.

Transcriptomics is the study of messenger ribonucleicacid (mRNA) production by cells under certain conditions.Because this is achieved in cell populations, in periodontalinvestigations either biopsies of relevant oral tissues or pe-ripheral blood leukocytes are used rather than oral fluids.This technique allows one to amplify the expressed geneproducts and maintains the stability and uniformity of theplatforms used to identify chemical species. Several find-ings have been reported. In a comparison of diseased andhealthy papillae from patients with advanced periodontitis,there were differences in gene ontology groups forapoptosis, antimicrobial humor responses, antigen presen-tation, regulation of metabolic groups, signal transduction,and angiogenesis. The differences in cell composition ofpapillae may yield different transcriptome profiles andcontribute to heterogeneous results. It was possible, how-ever, to identify genes not previously linked to periodontaldisease. In an investigation of gene expression changes inperiodontal tissues before and after treatment, gene pro-files that were altered the most reflected the activation ofpathways that regulate tissue damage and repair. Peri-odontal therapy was also noted to produce a systemicanti-inflammatory effect in a study of periodontitis andthe peripheral blood system. Overall, advances have beenmade, but the established data sets need to be gatheredtogether. Studies taking into account possible changes incell types within periodontal tissues are required to

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pinpoint genes that may differentiate between diseasetypes and identify useful biomarkers.

Proteomics is the study of all proteins within a sample.Mass spectrometry makes it possible to identify the variousprotein species in biologic samples, which often contain awide range of constituents. Often the most abundant pro-teins are removed or separated from a sample before anal-ysis, but proteomics also addresses the changes that occurin proteins. ‘‘Top-down’’ whole-protein approaches to iden-tify low-molecular-weight proteins have found humanneutrophil peptides in gingival crevicular fluid. ‘‘Bottom-up’’ approaches involve proteins digested to individualpeptides before tandem mass spectrometry techniquesare applied. These have discovered many novel insightsinto the periodontitis proteome. Two-dimensional electro-phoresis and liquid chromatography�mass spectrometrytechniques have also been used. Whole saliva has demon-strated differences in highly abundant proteins that wereincreased in diseased samples. Changes have also beennoted in previously uninvestigated proteins such as neutro-phil plastin-2, which is involved in Fcg receptor stimulation.However, no biomarkers have been validated.

Degradomics is a specialized area of proteomics that as-sesses the proteases at work in tissues involved in substrateprocessing, which is particularly applicable to periodontol-ogy. Protease activities have been noted in periodontitisusing this technique.

Metabolomics studies the quantities of all chemicalsexcept deoxyribonucleic acid (DNA), RNA, and proteins ina sample. Samples are analyzed using a battery of testsand separated by their chemical and physical properties,then identified usually using nuclear magnetic resonanceand mass spectrometry. One study in this area found thatlevels of metabolites from gingivitis sites were lower thanthose from healthy sites; this expanded the knowledgebase concerning sources of oxidative stress. Oxidative stressis acknowledged as an important contributor to peri-odontal disease. Lipidomics is a specialized area of metabo-lomics that focuses on the role of lipids in cellular function,since these substances integrate signaling and metabolicprocesses. Overall, metabolomics offers an area where

192 Dental Abstracts

intense research may help to clear up misunderstandingsabout periodontitis, especially concerning host and host–microflora interactions.

Systems biology integrates multiple ‘omic platforms anddata by reconstructing the complex networks involved.Often cell systems are studied, but to be relevant to peri-odontitis will require a study of the entire disease. Theinformation gathered through the various ‘omic technolo-gies requires coordination and integration, a major chal-lenge in the study of periodontal disease. Systems biologynow depends on the computational modeling of quantita-tive large-scale data sets gathered by ‘omic technologiesand the inference of biologic and artificial networks to un-derstand differences between health and disease. Futurestudies should build systems biology approaches into thedesign so information can be joined together and the un-derstanding of the contributions of multiple cell typesand underlying biology can be furthered.

Clinical Significance.—As yet, no validatedbiomarkers have been identified using thevarious ‘omic technologies. However, they areopening new routes for inquiry related to dis-ease pathogenesis. Because periodontitis is acomplex disease, it is likely that there are multi-ple biomarkers that could help differentiate be-tween health and disease or between diseaseonset and progression, that could improve theprognosis of the disease, and that could allowpatient stratification and the development ofindividualized interventions.

Grant MM: What do ‘omic technologies have to offer periodontalclinical practice in the future? J Periodont Res 47:2-14, 2012

Reprints available from MM Grant, Periodontal Research Group,School of Dentistry, Univ. of Birmingham, St. Chad’s Queens-way, Birmingham B4 6NN, UK; fax: þ44 121 237 2882; e-mail:m.m.grant@bham.ac.uk

Preventive DentistrySilver diamine fluoride for children’s caries

Background.—Children in the poorest areas of theworld suffer a high rate of untreated dental decay. Agentsto treat decay in community-based programs include silver

diamine fluoride (SDF) and interim restorative treatment(IRT). SDF is easy to apply, costs little, and improves the ac-cess to care for public health purposes. It has demonstrated