Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches

Adv Exp Med Biol. 2015;865:57-74. doi: 10.1007/978-3-319-18603-0_4.

Abstract

The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bacteroidaceae Infections / drug therapy*
  • Bacteroidaceae Infections / immunology
  • Bacteroidaceae Infections / microbiology
  • Bacteroidaceae Infections / pathology
  • Complement Activation / drug effects
  • Complement Inactivating Agents / therapeutic use*
  • Complement System Proteins / metabolism*
  • Disease Models, Animal
  • Dysbiosis / drug therapy*
  • Dysbiosis / immunology
  • Dysbiosis / microbiology
  • Dysbiosis / pathology
  • Host-Pathogen Interactions / drug effects
  • Humans
  • Macaca fascicularis
  • Mice
  • Peptides, Cyclic / therapeutic use
  • Periodontitis / drug therapy*
  • Periodontitis / immunology
  • Periodontitis / microbiology
  • Periodontitis / pathology
  • Porphyromonas gingivalis / immunology
  • Porphyromonas gingivalis / pathogenicity
  • Pyridones / therapeutic use
  • Receptors, Complement / antagonists & inhibitors*
  • Receptors, Complement / immunology
  • Receptors, Complement / metabolism

Substances

  • AcPhe(ornithine-Pro-cyclohexylamine-Trp-Arg)
  • Complement Inactivating Agents
  • Peptides, Cyclic
  • Pyridones
  • Receptors, Complement
  • 1-(ethan-1-ol)-2-methyl-3-hydroxypyridin-4-one
  • Complement System Proteins