THE DEVELOPMENT OF A NEW CLINICAL PARAMETER FOR DIAGNOSIS OF PERIODONTAL DISEASES AND THE NEW DRUG DESIGN

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Although a number of clinical parameters are now used for diagnosis of periodontal diseases, there exists the practical difficulty as to which parameters should be used to assess the rate of progress of the disease, the present disease activity and the need for treatment. is generally accepted that analysis of gingival crevicular fluid (GCF) can provide information of association between specific metabolic change and disease status and that a variety of proteolytic enzymes in GCF play an important role in pathogenesis of periodontal disease. The present work was designed to clarify the roles of lysosomal proteinases including cathepsins B, H, L, D, G, and medullasin in pathological destructive process of periodontal tissues and to put the knowledge of the GCF levels of these enzymes to practical use for diagnosis of periodontal diseases. For this purpose, we prepared the specific antibodies to each enzyme purified from human sources and determined the levels of enzymes in GCF from chronic adult periodontitis patients and experimental gingivitis subjects by enzyme immunoassay. The results indicate that the cysteine proteinases cathepsins B, H, and L are selectively released into gingival crevices at a relatively mild stage of periodontitis and their levels in GCF are positively correlated with the severity of the disease. However, no significant amounts of these enzymes are found in GCF from experimental gingivitis subjects. The serine proteinases medullasin and cathepsin G in GCF are also shown to increase with the severity of periodontitis and to decrease by periodontal treatment. Interestingly, large amounts of medullasin was detected in GCF from experimental gingivitis subjects. The results indicate that these lysosomal proteinases participate in the progression of periodontitis and that the dynamics of these enzymes in GCF is useul for determining the present disease activity and the disease progression.