| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
DeAngelis, Robert A. Abe, Toshiharu Lambris, John D. Hajishengallis, Evlambia Maekawa, Tomoki Hajishengallis, George Hosur, Kavita B. Ricklin, Daniel |
| Description |
Author Affiliation: Maekawa T ( Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104); Abe T ( Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104); Hajishengallis E ( Department of Preventive and Restorative Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104); Hosur KB ( Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104); DeAngelis RA ( Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.); Ricklin D ( Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.); Lambris JD ( Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 geoh@upenn.edu lambris@upenn.edu.); Hajishengallis G ( Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104) |
| Abstract |
Chronic periodontitis is induced by a dysbiotic microbiota and leads to inflammatory destruction of tooth-supporting connective tissue and bone. The third component of complement, C3, is a point of convergence of distinct complement activation mechanisms, but its involvement in periodontitis was not previously addressed. We investigated this question using two animal species models, namely, C3-deficient or wild-type mice and nonhuman primates (NHPs) locally treated with a potent C3 inhibitor (the compstatin analog Cp40) or an inactive peptide control. In mice, C3 was required for maximal periodontal inflammation and bone loss, and for the sustenance of the dysbiotic microbiota. The effect of C3 on the microbiota was therefore different from that reported for the C5a receptor, which is required for the initial induction of dysbiosis. C3-dependent bone loss was demonstrated in distinct models, including Porphyromonas gingivalis-induced periodontitis, ligature-induced periodontitis, and aging-associated periodontitis. Importantly, local treatment of NHPs with Cp40 inhibited ligature-induced periodontal inflammation and bone loss, which correlated with lower gingival crevicular fluid levels of proinflammatory mediators (e.g., IL-17 and RANKL) and decreased osteoclastogenesis in bone biopsy specimens, as compared with control treatment. To our knowledge, this is the first time, for any disease, that complement inhibition in NHPs was shown to inhibit inflammatory processes that lead to osteoclastogenesis and bone loss. These data strongly support the feasibility of C3-targeted intervention for the treatment of human periodontitis. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| DOI |
10.4049/jimmunol.1400569 |
| Journal |
The Journal of Immunology |
| Issue Number |
12 |
| Volume Number |
192 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2014-06-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Bacteroidaceae Infections Bone Resorption Complement C3 Periodontitis Porphyromonas Gingivalis Immunology Pyridones Pharmacology Animals Drug Therapy Genetics Pathology Antagonists & Inhibitors Disease Models, Animal Inflammation Mediators Macaca Fascicularis Mice Osteoclasts Peptides, Cyclic Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
