October 1, 2001

Deficiency in White Blood Cell Function Leads to Severe Periodontal Disease

Scientists supported by the NIDCR have offered the first direct, physical evidence that a deficiency in white blood cell function can lead to early-onset periodontal disease, or aggressive periodontitis.  The conclusion comes from studies of genetically engineered mice that are unable to fight periodontal infections.

This study is significant because until now, researchers have shown only an association --  not a direct cause-and-effect relationship  --  between a deficiency in the functioning of white blood cells and early-onset periodontal disease," said the study’s lead author Richard Niederman, D.M.D., from the Department of Cytokine Biology at The Forsyth Institute in Boston.  The scientists showed that at six weeks of age the genetically engineered mice had lost 25 percent of their alveolar bone whereas the normal mice had no bone loss.  The loss of alveolar bone, which anchors teeth in place, is a hallmark of periodontitis.  The authors published their findings in the June issue of the Journal of Clinical Periodontology.

Early-onset periodontal disease affects between 1 percent and 10 percent of the U.S. population.  It is an infectious disease that involves rapid destruction of alveolar bone and attachment loss of gums from the teeth.  Without treatment, teeth can become loose and fall out.  Researchers believe this form of periodontal disease may be inherited.

Mouse Model Provides Evidence

To study aggressive periodontitis, the scientists used a mouse model created at the Massachusetts Institute of Technology that mimics a human disorder called leukocyte adhesion deficiency type II.  In the mouse model, genes for two proteins -- called selectins -- are ‘knocked out.’  Without these proteins, infection-fighting white blood cells are unable to latch onto the side of blood vessel walls and then leave the bloodstream and travel to sites of infection.  "Our work validates the use of this animal model for studying early onset periodontal disease," said Dr. Niederman.  "Additionally, this is the only animal model in which the aggressive form of gum disease develops spontaneously and very quickly."

The scientists also provided evidence that bacteria are necessary to initiate the disease process.  To test this theory, they gave antibiotics to some of the knockout mice.  The antibiotics reduced the amount of bacteria and eliminated alveolar bone loss in the knockout mice.  The scientists said this indicates that bacteria are required for early onset periodontal disease to develop.  "We think that the decreased ability of the white blood cells to reach infection sites permits overgrowth of all bacteria, including harmful types," said Dr. Niederman.  "Bone loss may be initiated when the amount of harmful bacteria rises above a certain level."

The current research builds on earlier work by the Forsyth team and other scientists who have studied the cellular and molecular basis of aggressive periodontitis.  Future work by the researchers at Forsyth will focus on using the mouse model to study host-bacterial interactions as well as possible genetic factors that influence disease development and progression.  Specifically, the research team is studying the genetics of both the host and the infecting organisms.  Working with Dr. Niederman at Forsyth are Dr. Phil Stashenko, Department of Cytokine Biology, and Drs. Floyd Dewhirst and Bruce Paster, Department of Molecular Genetics.

The National Heart, Lung and Blood Institute and the Howard Hughes Medical Institute provided additional support for this research.

Back to NIDCR Research Digest