MURINE MODEL OF LAD II/EARLY ONSET PERIODONTITIS

牙周病是牙周组织的炎症性感染

Periodontal disease is an inflammatory infection of the periodontium which results in alveolar bone loss. Evidence from a number of laboratories indicates that the incidence of early onset periodontal disease (before age 20) is high (greater than 2 percent of the US population), and may be due to defects in leukocyte function. Of particular relevance to this application are the human leukocyte adhesion deficiencies termed LAD-II. Patients with these disorders display specific defects in the selectin ligand adhesion molecules. They also exhibit severe infections, including early onset periodontal disease. Like other forms of early onset periodontal disease, it is postulated, but not proven, that LAD is responsible for the observed aggressive periodontal disease. In the studies proposed in this application we will directly test this hypothesis. Genetically- engineered mice simultaneously deficient in two adhesion molecules (P- /E-selectin, LAD-II equivalent) will be used for these experiments. Age, gender, and strain matched wild type mice will serve as controls. Three different experimental approaches will be utilized. 1. Naturally occurring periodontal bone loss will be determined morphometrically and histologically. 2. The naturally occurring periodontal bacteria will be identified, and correlated with alveolar bone loss. 3. The correlated periodontal cellular inflammatory infiltrate and inflammatory cytokine responses will be determined. These studies will characterize the first animal model system for naturally-occurring early onset periodontal disease. They also will establish the role of the leukocyte selectin adhesion molecules in this disease. Thus, the proposed studies will provide a better understanding of periodontal disease pathogenesis, and more broadly, infectious diseases in general. They may also suggest ways to prevent their progress.