Biomarkers of Periodontal Disease Progression

Inclusion Criteria: General Inclusion Criteria To be eligible to participate in this study, a subject must meet all of the following criteria: 1. Ability to understand, and willingness and ability to read and sign, the informed consent form. 2. Age of at least 25 years. 3. Ability to understand and follow directions for study procedures. 4. Minimum of 20 natural teeth, excluding third molar teeth; at least 12 of these teeth must be pre-molars, first molars, or second molars. 5. Willingness not to have professional dental prophylaxis or scaling for the duration of the disease progression and monitoring phase (12 months). 6. Willingness to comply with all study procedures and be available for the duration of the study. 7. For women with reproductive potential, willingness to use highly effective contraception (e.g., licensed hormonal contraception, intrauterine device, abstinence, or vasectomy in partner). Specific inclusion criteria: Healthy periodontal subjects must have: 1. Any tooth with 3 mm or less PD, irrespective of the attachment level, will be acceptable 2. No teeth with PD of 4 mm or more and concomitant attachment loss, with the exception of the distal of the second molars where a PD of 4 mm and concomitant CAL of up to 2 mm will be acceptable. 3. No radiographic evidence of alveolar bone loss (defined as a distance of greater than 2.0 mm measured radiographically from the CEJ to the crest of the alveolar bone); with the exception of the mandibular incisors where up to 3.0 mm of alveolar bone loss measured radiographically from the CEJ to the crest of the alveolar bone will be accepted. Mild periodontal disease subject: periodontal loss must meet the following criteria and must not meet the minimum criteria for severe periodontal loss: 1\. At least 4 teeth with at least 1 site of PD of 5 mm or more and concomitant CAL greater than or equal to 2 mm, and radiographic evidence of mesial or distal alveolar bone loss around at least 2 of the affected teeth. Alveolar bone loss is defined as a distance of \> 2.0 mm measured radiographically from the CEJ to the crest of the alveolar bone. Subjects with severe periodontal loss must meet all of the following criteria: 1\. At least 8 separate teeth with at least 1 site of PD of 5 mm or more and concomitant CAL greater than or equal to 3 mm, and radiographic evidence of mesial or distal alveolar bone loss around at least 2 of the affected teeth. Alveolar bone loss is defined as a distance of \> 2.0 mm measured radiographically from the CEJ to the crest of the alveolar bone. Exclusion Criteria: 1. Presence of orthodontic appliances. 2. The following conditions noted on oral examination: * Oral lichen planus * Candidiasis * Clinical leukoplakia * Clinical erythroplakia * Pemphigus * Pemphigoid * Other recurrent intraoral or perioral vesiculobullous diseases * Aphthous ulcerations (major or minor). Subjects presenting with aphthous ulcers should be rescreened after 2 weeks. They will be eligible if the ulcers have healed and the subject does not have a history of frequent recurrences. * Herpetic lesions. Subjects presenting with herpes labialis or intraoral herpes should be rescreened after 2 weeks. They will be eligible if the lesions have healed and the subject does not have a history of frequent recurrences. j. Traumatic ulcers. If a subject presents with a traumatic ulcer, he/she can be rescreened in 2-3 weeks. The subject will be eligible if the ulcers have healed. 3. Acute necrotizing ulcerative gingivitis or gross tooth decay, as determined by the investigator. 4. Root fragments, pericoronitis, endo-perio lesions, or other dental abscesses. Subjects may be rescreened after resolution of these dental conditions. 5. Pregnancy or lactation. 6. Requirement for prophylactic antibiotics for dental procedures (e.g., for certain heart and orthopaedic conditions\*). 7. Periodontal or systemic antibiotic therapy in the previous 6 months. Routine dental prophylaxis will be allowed. 8. Use of cigarettes or other tobacco products within 1 year before the screening visit. 9. Any medical condition that might influence the course of periodontal disease or treatment (e.g., diabetes \[irrespective of level of control\], human immunodeficiency virus infection or acquired immunodeficiency syndrome, use of medications associated with gingival hyperplasia). 10. Chronic use of nonsteroidal anti-inflammatory drugs (e.g., for arthritis), defined as the need, or anticipated need, for over 3 weeks of continuous use at the time of enrollment or during the course of the study. The use of low-dose aspirin (81 mg/day) for prophylaxis will be allowed. 11. Current or anticipated use of chronic systemic corticosteroids, cyclosporine, or other systemic immunosuppressive agent. The use of inhaled corticosteroids will be allowed. 12. Hypersensitivity to tetracyclines (e.g., tetracycline, doxycycline, minocycline). 13. Participation in a clinical study testing a drug, biologic, device, or other intervention within the last 30 days. 14. Any condition or circumstance that, in the opinion of the investigator, would place the subject at increased risk or preclude his/her full compliance with or completion of the study.