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

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.