Possible role of TNF-α in osteoclastogenesis in the presence or absence of <i>P. gingivalis</i>.

<p>Macrophages respond to infection with <i>P. gingivalis</i> by producing TNF-α, which stimulates osteoclastogenesis in osteoclast precursor cells in the absence of <i>P. gingivalis</i> (A). However, osteoclast precursor cells primed with RANKL do not produce TNF-α and respond differentially to various stimuli. (B) Cells that are not stimulated do not differentiate into osteoclasts. (C) Cells that are continuously re-stimulated with RANKL differentiate into osteoclasts in an NFATc1- and NF-κB-dependent manner in the presence of <i>P. gingivalis</i>. (D) Cells that are infected with <i>P. gingivalis</i> differentiate into osteoclasts in an NFATc1-dependent and NF-κB-independent manner. TNF-α does not stimulate osteoclastogenesis in osteoclast precursor cells in the presence of <i>P. gingivalis</i>, whereas RANKL stimulates osteoclastogenesis in the presence or absence of <i>P. gingivalis</i>.