ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Genetic and intervention studies implicating complement C3 as a major target for the treatment of periodontitis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Salivary Proteomics for Detecting Novel Biomarkers of Periodontitis: A Systematic Review.Journal of periodontal research · 2025Pooled it
- Phase IIa clinical trial of complement C3 inhibitor AMY-101 in adults with periodontal inflammation.The Journal of clinical investigation · 2021Trial
- Exacerbation of inflammatory bone loss in TET2-driven clonal hematopoiesis.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- IL-22 synergizes with IL-17 to promote mucosal inflammation and bone loss.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Exoproteome of calorie-restricted humans identifies complement deactivation as an immunometabolic checkpoint reducing inflammaging.Nature aging · 2026Article
- Article
- Interaction between serum levels of Porphyromonas gingivalis immunoglobulin G and lutein/zeaxanthin is associated with risk for age-related macular degeneration.Scientific reports · 2025Article
- AMY-101 as complement C3 inhibitor for periodontitis therapy: mechanisms, efficacy, and clinical translation.Frontiers in immunology · 2025Review
- Article
- A guide to complement biology, pathology and therapeutic opportunity.Nature reviews. Immunology · 2024Review
- Association between dysbiotic perio-pathogens and inflammatory initiators and mediators in COVID-19 patients with diabetes.Heliyon · 2024Article
- Changes in the components of salivary exosomes due to initial periodontal therapy.Journal of periodontal & implant science · 2023Article
- The Complement-Targeted Inhibitor Mini-FH Protects against Experimental Periodontitis via Both C3-Dependent and C3-Independent Mechanisms.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Illuminating the oral microbiome and its host interactions: animal models of disease.FEMS microbiology reviews · 2023Review
- Neutrophils in the periodontium: Interactions with pathogens and roles in tissue homeostasis and inflammation.Immunological reviews · 2023Review
- Strategies of cell and cell-free therapies for periodontal regeneration: the state of the art.Stem cell research & therapy · 2022Review
- Oral characteristics in adult individuals with periodontal Ehlers-Danlos syndrome.Journal of clinical periodontology · 2022Article
- Complement Is Required for Microbe-Driven Induction of Th17 and Periodontitis.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Osteoporosis and periodontal diseases - An update on their association and mechanistic links.Periodontology 2000 · 2022Review
- Osteoimmunology in Periodontitis: Local Proteins and Compounds to Alleviate Periodontitis.International journal of molecular sciences · 2022Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.