Inhibition of T-Cell-Mediated and infection-Induced periodontal bone resorption by TACE blockade

Abstract

Host immune responses trigger promotion of bone resorption in periodontitis, and infiltrated lymphocytes express abundant RANKL, the essential factor for osteoclastogenesis. Since RANKL is initially produced as a membrane- bound protein, cell-to-cell contact can be required for osteoclastogenesis. However, distance between lymphocytes and active osteoclasts is generally observed. This observation presume released cytokine(s) from activated lymphocytes might induce osteoclastogenesis in periodontitis. Previously, we reported that cleavage of RANKL and TNF-α by TNF-α converting enzyme (TACE) from lymphocytes can play a role in human periodontitis. Herein, we further examined function of TACE in two experimental periodontitis models in rats: (1) Aggregatibacter actinomycetemcomitans-reactive T-cell adop- tive transfer and (2) Porphyromonas gingivalis infection. Anti-TACE antibody was injected into the gingivae to probe the role of TACE in bone destruction. Our data suggested that TACE blockade could inhibit alveolar bone destruction. TACE might be a potentially therapeutic target for periodontitis amelioration.