INDUCTION OF APOPTOSIS IN MURINE CLONAL OSTEOBLASTS EXPRESSED BY HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I TAX BY NF-KAPPA-B AND TNF-ALPHA

We investigated the effects of various cytokines in the presence of hu man T-cell leukemia virus type I (HTLV-I) tax protein in murine clonal osteoblasts, MC3T3-E1 cells, Skeletal remodeling by osteoclasts and o steoblasts is coordinated by cytokines, which are activated by HTLV-I tax protein via nuclear factor-kappa B (NF-kappa B). MC3T3-E1 cells we re cocultured with an irradiated HTLV-I-producing lymphocyte cell line , MT-2, After coculture, the tumor necrosis factor-alpha (TNF-alpha) l evel in the medium was markedly elevated during the 7 days of culture, and MC3T3-E1 cells underwent apoptotic cell death, Marked apoptosis w as also observed in MC3T3-E1 cells treated with MT-2 culture medium an d in HTLV-I tax-expressing MC3T3-E1 clones, which both expressed high levels of TNF-alpha. This apoptosis was prevented by treatment with ne utralizing anti-TNF-alpha antibody (alpha TNF), HTLV-I tax protein and TNF-alpha induced activation of NF-kappa B in apoptotic MC3T3-E1 cell s, Decreased NF-kappa B activation was observed in HTLV-I tax-expressi ng MC3T3-E1 cells treated with alpha TNF, Our results suggest that HTL V-I tax activated NF-kappa B and subsequently TNF-alpha, leading to ap optosis of osteoblasts.