Diagnostic strategies of periodontitis based on the molecular mechanisms of periodontal tissue destruction.

Abstract

Periodontitis is a disease showing differences in disease progression between patients and between sites within a patient. Routine clinical examinations today are not useful enough to distinguish susceptible patients and active lesions from resistant patients and chronic lesions. Diagnostic markers should be pathogenic and inflammatory factors participating in periodontal tissue destruction. These are both local and systemic factors. First of all, pathogenic factors and proinflammatory cytokines or mediators in gingival crevicular fluid (GCF) were examined and the difference was found between active and inactive periodontitis lesions distinguished by attachment loss. Active lesions were detected by discriminant-function analysis of these examinations, although the sensitivity of differential diagnosis was low. Then, we established a novel needle biopsy for understanding the pathophysiological conditions elicited in active and chronic inflammatory processes of periodontal tissue destruction. A variety of cytokines and mediators were detected in biopsied specimens by reversed transcription polymerase chain reactions (RT-PCR). Cytokine profiles were varied in inflammed periodontal biopsies. As IFN gamma mRNA expression was enhanced in inflamed gingiva, antigen-presenting-cell (APC) functions of human gingival fibroblasts (HGF) were examined. Despite the phenotypical resemblance of IFN gamma-treated HGF to so-called APC, HLA-DR positive HGF could not induce proliferation but suppressed proliferation of alloreactive peripheral blood T cells (PBT). However, HLA-DR positive HGF stimulated the proliferative responses of PBT which had been primed with allo-APC. Regulatory immune responses by IFN gamma were different in T cell conditions. Various kinds of cytokines participated in periodontal inflammation, and every cytokine is multi-functional. Complex and compound inflammatory processes can be clarified by examining cytokine networks and the precise effects of each cytokine on each of the cell types comprising periodontal tissue. It is, therefore, necessary for establishing diagnostic strategies to integrate pathogenic and inflammatory factors in periodontal tissue destruction.