Objectives: Recently, g-glutamyl transpeptidase (GGT) was identified as a novel bone resorbing factor. It was also reported that GGT was up-regulated in synovial fluid of rheumatoid arthritis. These findings indicate a possibility that GGT is a potent risk factor of periodontitis. However, little is known about relationship between GGT and periodontitis. The aim of this study was to examine the role of GGT on alveolar bone destruction (AB-destruction) associated with periodontitis.
Methods: 1) GGT (50mg/ml) was applied into rat gingival sulcus of upper molars and periodontal tissue was histologically examined. Proinflammatory cytokine-mRNA expression in gingival tissues was analyzed by RT-PCR. Inhibitory effect of GGT antibody (AGT) pretreatment was also examined. 2) To examine the effect of hyper-GGTemia on AB-destruction, rat bile duct ligation (BDL) model with hyper-GGTemia was examined. 3) Expression levels of genes related to bone resorption were examined in GGT (100ng/ml)-stimulated ST2 cells. 4) GCF was collected from periodontitis patients at the initial visit using paper point. GGT-activity in GCF was analyzed by GGT-activity measurement kit (AC Bio). Periodontal pocket depth (PPD) and alveolar bone resorption rate (%ABR) at GCF-collected area were also measured.
Results: 1) Topically applied GGT increased osteoclasts along the bone margin (P<0.01). In GGT-applied gingival tissues, up-regulation of TNF-a mRNA and IL-1b was evident. Meanwhile AGT-pretreatment suppressed osteoclasts induced by GGT. 2) In BDL-animals having hyper-GGTemia, increase of osteoclasts was observed. 3) In vitro study, GGT up-regulated mRNA expression of TNF-a, IL-1b and RANKL and down-regulated that of OPG in ST2 cells. 4) There was a positive correlation between GGT-activity in GCF and %ABR (r=0.854). Moreover, GGT-activity was generally reduced by initial periodontal therapy.
Conclusion: GGT is a potent risk factor of AB-destruction. GGT-activity in GCF can be an indicator for disease activity of periodontitis and a novel therapy targeting GGT may be expected.