title: Prevention of inflammation-mediated bone loss in murine and canine periodontal disease via recruitment of regulatory lymphocytes.
abstract: The hallmark of periodontal disease is the progressive destruction of gingival soft tissue and alveolar bone, which is initiated by inflammation in response to an invasive and persistent bacterial insult. In recent years, it has become apparent that this tissue destruction is associated with a decrease in local regulatory processes, including a decrease of forkhead box P3-expressing regulatory lymphocytes. Accordingly, we developed a controlled release system capable of generating a steady release of a known chemoattractant for regulatory lymphocytes, C-C motif chemokine ligand 22 (CCL22), composed of a degradable polymer with a proven track record of clinical translation, poly(lactic-co-glycolic) acid. We have previously shown that this sustained presentation of CCL22 from a point source effectively recruits regulatory T cells (Tregs) to the site of injection. Following administration of the Treg-recruiting formulation to the gingivae in murine experimental periodontitis, we observed increases in hallmark Treg-associated anti-inflammatory molecules, a decrease of proinflammatory cytokines, and a marked reduction in alveolar bone resorption. Furthermore, application of the Treg-recruiting formulation (fabricated with human CCL22) in ligature-induced periodontitis in beagle dogs leads to reduced clinical measures of inflammation and less alveolar bone loss under severe inflammatory conditions in the presence of a diverse periodontopathogen milieu.
authors.affiliation: Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA 15261.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Glowacki
authors.forename: Sayuri
authors.initials: S
authors.lastname: Yoshizawa
authors.forename: Siddharth
authors.initials: S
authors.lastname: Jhunjhunwala
authors.forename: Andreia E
authors.initials: AE
authors.lastname: Vieira
authors.forename: Gustavo P
authors.initials: GP
authors.lastname: Garlet
authors.forename: Charles
authors.initials: C
authors.lastname: Sfeir
authors.forename: Steven R
authors.initials: SR
authors.lastname: Little
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000187:drug effects; D016301:Alveolar Bone Loss / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control*; D000818:Animals; D054422:Chemokine CCL22 / Q000008:administration & dosage / Q000494:pharmacology*; D003692:Delayed-Action Preparations / Q000494:pharmacology; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods*; D019344:Lactic Acid; D051379:Mice; D010518:Periodontitis / Q000150:complications* / Q000382:microbiology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016966:Porphyromonas gingivalis / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D054422:Chemokine CCL22; D003692:Delayed-Action Preparations; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid