Role of transcriptional factor activation protein-1 in endogenous expression of the interleukin-1 beta gene involved in Porphyromonas gingivalis fimbria-stimulated bone resorption in the mouse calvarial system.

We previously suggested that endogenous interleukin-1 beta (IL-1 beta) produced by Porphyromonas gingivalis fimbriae stimulation in calvarial bone cell cultures plays a role in bone resorption as a major cytokine. Therefore, in the present study, we initiated experiments to clarify the stimulatory mechanism of IL-1 beta gene expression in fimbria-stimulated bone resorption. Fimbria-stimulated bone resorption was dramatically inhibited by curcumin, a potent inhibitor of activation protein-1 (AP-1). In fact, the fimbriae induced markedly both the expression of c-fos and c-jun genes and their protein production in the calvarial cells. In addition, a mixture of antisense oligonucleotides against c-fos and c-jun significantly inhibited not only the fimbria-induced expression of the IL-1 beta gene but also the fimbria-induced bone resorption. Therefore, the present study demonstrates that transcriptional factor AP-1 plays a functional role in P. gingivalis fimbria-stimulated bone resorption via endogenous IL-1 beta in the mouse calvarial system.