IL-12-mediated and IL-18-mediated Nitric oxide-induced apoptosis of adherent bone marrow cells in TNF-α-induced osteoclast formation

It has recently been reported that TNF-a has the ability to accelerate osteoclastogenesis. We previously reported that the proinflammatory cytokine IL-12 and IL-18 induced apoptosis in TNF-α-mediated osteoclastogenesis in mouse bone marrow culture through an interaction of Fas and Fas ligand (FasL). However, the inhibition of Fas-FasL interaction by using anti-FasL antibody could not completely inhibit apoptosis. Therefore, it is possible that IL-12 and IL-18 may also trigger some other apoptotic mechanisms. Nitric oxide (NO) may act as a mediator of the apoptotic effect. We found that NO production was induced in bone marrow cells cultured with IL-12 and IL-18 in the presence of TNF-α. Apoptosis was partially inhibited when bone marrow cells were treated with NO inhibitors. The simultane- ous effects of TNF-α and IL-12 or IL-18 on bone marrow cells induce apoptosis by the production of NO.