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J Clin Periodontol. 2016 Mar;43(3):238-49. doi: 10.1111/jcpe.12507. Epub 2016 Mar 3.

Inhibition of pre-existing natural periodontitis in non-human primates by a locally administered peptide inhibitor of complement C3.

Author information

1
Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
2
Research Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
3
College of Dentistry, Manila Central University, Caloocan City, Philippines.
4
Simian Conservation Breeding and Research Center (SICONBREC), Makati City, Philippines.
5
Division of Pediatric Dentistry, Department of Preventive and Restorative Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
6
Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Abstract

AIM:

Human periodontitis is associated with overactivation of complement, which is triggered by different mechanisms converging on C3, the central hub of the system. We assessed whether the C3 inhibitor Cp40 inhibits naturally occurring periodontitis in non-human primates (NHPs).

MATERIALS AND METHODS:

Non-human primates with chronic periodontitis were intra-gingivally injected with Cp40 either once (5 animals) or three times (10 animals) weekly for 6 weeks followed by a 6-week follow-up period. Clinical periodontal examinations and collection of gingival crevicular fluid and biopsies of gingiva and bone were performed at baseline and during the study. A one-way repeated-measures anova was used for data analysis.

RESULTS:

Whether administered once or three times weekly, Cp40 caused a significant reduction in clinical indices that measure periodontal inflammation (gingival index and bleeding on probing), tissue destruction (probing pocket depth and clinical attachment level) or tooth mobility. These clinical changes were associated with significantly reduced levels of pro-inflammatory mediators and decreased numbers of osteoclasts in bone biopsies. The protective effects of Cp40 persisted, albeit at reduced efficacy, for at least 6 weeks following drug discontinuation.

CONCLUSION:

Cp40 inhibits pre-existing chronic periodontal inflammation and osteoclastogenesis in NHPs, suggesting a novel adjunctive anti-inflammatory therapy for treating human periodontitis.

KEYWORDS:

complement; compstatin; cytokines; inflammation; non-human primates; periodontitis

PMID:
26728318
PMCID:
PMC4803614
[Available on 2017-03-03]
DOI:
10.1111/jcpe.12507
[Indexed for MEDLINE]
Free PMC Article

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