Periodontal disease is characterized by the loss of connective tissue and alveolar bone. The loss of these tissues is initiated by oral bacterial that induce an inflammatory cascade leading to the destructive events. While the molecular actions that result in lysis of connective tissue matrix and bone resorption have been well defined, it is not known why the repair mechanisms present in both tissues are not effective in restoring the damage which occurs. Thus, the two clinically significant events in periodontitis, net loss of attachment and alveolar bone, can be linked to inadequate repair after bacteria-induced damage. That one of the characteristic changes that occurs in episodes of recent periodontal breakdown is the loss of fibroblasts suggests that apoptosis may be an important antecedent to the net tissue loss. Preliminary data indicate that the super-periosteal injection of P. gingivalis, a prominent periodontal pathogen, into the scalp causes marked inflammation, destruction of connective tissue matrix followed by infiltration and proliferation of fibroblastic cells. Likewise, bone resorption occurs followed by the formation of new woven bone. We will use this model to examine the events that occur following P. gingivalis infection focusing on apoptosis and repair. The goal for the proposed studies is to test the hypothesis that periodontal pathogens induce apoptosis of critical cells and thereby impede normal repair of bone and connective tissue matrix. We propose that induced apoptosis is mediated via TNF-induced caspase activity. These studies will provide new insight into the mechanisms for a net loss of periodontal tissues taking an approach that has not been previously applied to this problem.
