The enduring importance of animal models in understanding periodontal disease

Abstract

Whereas no single animal model can reproduce the complexity of periodontitis, different aspects of the disease can be addressed by distinct models. Despite their limitations, animal models are essential for testing the biological significance of in vitro findings and for establishing cause-and-effect relationships relevant to clinical observations, which are typically correlative. We provide evidence that animal-based studies have generated a durable framework for dissecting the mechanistic basis of periodontitis. These studies have solidified the etiologic role of bacteria in initiating the inflammatory response that leads to periodontal bone loss and have identified key mediators (IL-1, TNF, prostaglandins, complement, RANKL) that induce inflammatory breakdown. Moreover, animal studies suggest that dysbiosis, rather than individual bacterial species, are important in initiating periodontal bone loss and have introduced the concept that organisms previously considered commensals can play important roles as accessory pathogens or pathobionts. These studies have also provided insight as to how systemic conditions, such as diabetes or leukocyte adhesion deficiency, contribute to tissue destruction. In addition, animal studies have identified and been useful in testing therapeutic targets.

Keywords: animal models; dysbiosis; immune subversion; inflammation; periodontitis; systemic disease.

Figure 1.

Animal models of periodontitis: characteristics and contributions. Animal models are contrasted with in vitro models and human studies in terms of their advantages and disadvantages, followed by a summary of key animal model-based contributions to understanding periodontal disease pathogenesis. It should be noted, however, that animal model-based research benefits from both in vitro models and human studies for obtaining mechanistic insights in finer molecular detail and for determining clinical relevance, respectively. The cycle connecting the 3 experimental systems is meant to demonstrate this interrelationship. For instance, the arrows emanating from “Animal models” and “Human studies” to “In vitro models” indicate the reliance of the former systems on the more tractable in vitro system for dissecting plausible molecular mechanisms. Conversely, the reverse arrows indicate that in vitro model-based mechanisms depend on animal and human systems for testing potential biological relevance. One of the greatest contributions of animal models is the testing of cause-and-effect relationships that cannot be typically addressed in human studies, most of which are correlative. Conversely, candidate drugs identified in animal models require the ultimate test in human clinical trials before they can be validated and enter the clinic.