1. Pathobiology of the Periodontal Tissues Mark C. Herzberg Department of Oral Sciences

2. A classification of periodontal diseases Diagnosis gingivitis periodontitis –juvenile localized generalized –adult Characteristics Infection -> inflammation Loss of alveolar bone Clinical considerations age of onset rate of progression severity sites affected

3. Epidemiology of periodontal diseases Estimated 20 to 60% of adults affected in US Prevalence and severity –unrelated to dental caries history –inversely related to education, urbanization, economic status –increases with age (NO C-E relationship) Principally associated with quality of oral hygiene Juvenile and rapidly progressive lesions seen before age 40 Risk factors vs. cause (etiology)

4. Transition from health to periodontitis Periodontitis is typically a chronic infection Loss of epithelial attachment and resorption of alveolar bone

5. Transition from health to periodontitis Periodontitis and gingivitis are infections that cause inflammation Gingivitis marked by inflamed gingiva without measureable loss of alveolar bone

6. Transition from health to periodontitis Gingivitis and periodontitis caused by microorganisms in dental plaque Plaque can reside on or in calculus (‘tarter’)

7. Transition from health to periodontitis Gingivitis and periodontitis are different infections Gingivitis typically does not progress to periodontitis Periodontal diseases, therefore, are a set of infections that affect the supporting structures of the teeth

8. Transition from health to periodontitis: gingivitis Attached gingiva in caucasians is pale pink With inflammation, the crestal or marginal gingiva becomes increasingly red Microscopically, attached epithelium attracts large numbers of inflammatory, white blood cells 43-yr old woman Microscopic appearance beagle dog

9. Transition from health to periodontitis recession exudate gingival inflammation varies bony crater exposed Post-surgical treatment

10. Transition from health to periodontitis Proliferation of epithelial attachment Loss of alveolar bone Disruption of connective tissue attachment Inflammatory cell infiltrate X-ray bone lossCryptic infection

11. Age of onset of periodontitis Heinz-Mayfield et al. J Clin Perio 30:902, 2003

12. Frequency of sites with 2mm or greater attachment loss Younger than 25 yrs 55 yrs or older Heinz-Mayfield et al. J Clin Perio 30:902, 2003

13. Subgingival dental plaque Dental plaque is a complex community of microbes - biofilm When attached to the tooth (or root as shown here), the community can exist in different architectural forms

14. Uncovering causative microorganisms Indigenous infection Compromised host Opportunistic Commensal Prevotella intermedia Fusobacterium spp. Peptostreptococcus micros Eubacterium spp. Spirochetes Campylobacter rectus Bacteroides forsythus Exogenous infection Healthy carrier Superinfection ‘True’ infection enteric rods Actinobacillus Pseudomonads actinomycetemcomitans Staphylococci Porphyromonas Candida spp. gingivalis

15. Examples of Syndromic Forms of Periodontitis in Which Inheritance is Mendelian and Due to a Genetic Alteration at a Single Gene Locus Papillon-Lefèvre syndrome Haim-Munk syndrome Ehlers-Danlos syndrome type 4 Ehlers-Danlos syndrome 8 Cyclic neutropenia Chronic familial neutropenia Chediak-Higashi syndrome Congenital disorder of glycosylation type IIc Leukocyte adhesion deficiency Adapted from Kinane & Hart. CROBM 14:230, 2003

16. The classic relationship among phenotype, environment, and genotype For the periodontal disease phenotype, environmental risk factors include: smoking status plaque control socio-economic status diabetes,... Phenotype = environment + genotype + genotype x environment G x E is the interaction between environment and genotype (includes gene-gene interactions). Adapted from Kinane & Hart. CROBM 14:230, 2003

17. Is periodontitis in healthy adults a genetic disease? Yes, but genetics may be reflected in the relative susceptibility or resistance. Identical twins raised together and apart were compared for clinical expression of periodontitis. 50 to 70% of the variability in clinical expression was attributable to genetics. Michalowicz et al. J Periodontol 62:293, 1991 The search for genetic markers, polymorphisms, SNPs, mutations, … is in progress.

18. Host response to periodontal infection: bone loss Modified from Teng. CROBM 14:237, 2003 Direct invasion of host cells Matrix-degrading enzymes T-cell response Pro-inflammatory cytokines Plaque

19. Paquette et al, 1999

24. Pathobiology of periodontal diseases Complex infection initiated by microorganisms in dental plaque causing inflammatory diseases Genetics appear to contribute to clinical expression of disease Risk factors such as smoking, diabetes are strongly associated Host response may be both protective and destructive ‘Local’ periodontitis linked to systemic diseases: pathogen load, cytokine signaling, …