Induction of apoptosis in murine clonal osteoblasts expressed by human T-cell leukemia virus type I tax by NF-κPB and TNF-α

Abstract

We investigated the effects of various cytokines in the presence of human T‐cell leukemia virus type I (HTLV‐I) tax protein in murine clonal osteoblasts, MC3T3‐E1 cells. Skeletal remodeling by osteoclasts and osteoblasts is coordinated by cytokines, which are activated by HTLV‐I tax protein via nuclear factor‐κB (NF‐κB). MC3T3‐E1 cells were cocultured with an irradiated HTLV‐I‐producing lymphocyte cell line, MT‐2. After coculture, the tumor necrosis factor‐α (TNF‐α) level in the medium was markedly elevated during the 7 days of culture, and MC3T3‐E1 cells underwent apoptotic cell death. Marked apoptosis was also observed in MC3T3‐E1 cells treated with MT‐2 culture medium and in HTLV‐I tax‐expressing MC3T3‐E1 clones, which both expressed high levels of TNF‐α. This apoptosis was prevented by treatment with neutralizing anti‐TNF‐α antibody (αTNF). HTLV‐I tax protein and TNF‐α induced activation of NF‐κB in apoptotic MC3T3‐E1 cells. Decreased NF‐κB activation was observed in HTLV‐I tax‐expressing MC3T3‐E1 cells treated with αTNF. Our results suggest that HTLV‐I tax activated NF‐κB and subsequently TNF‐α, leading to apoptosis of osteoblasts.