肿瘤坏死因子α对ROS17/2.8细胞甲状旁腺素受体的下行调节

Down Regulation of PTH Receptor in ROS 17/2.8 Cells by Tumor Necrotic Factor Alpha

肿瘤坏死因子α(TNFα)是激活的单核巨噬细胞分泌的蛋白质,分子量17kD。其多功能性和选择性抑制肿瘤细胞生长的作用受到高度重视。我们的实验表明:TNFα(3×10^(-10)-1×10^(-7)mol/L)能显著降低大鼠成骨肉瘤细胞株ROS17/2.8的甲状旁腺素(PTH)受体总结合率,比对照降低7.47-37.45％,且与TNFα的浓度呈正相关。时间曲线显示,TNFα作用时间越长,受体总结合率降低越明显。Scatchard作图表明PTH受体数目降低而其亲和力无显著变化。细胞周期分析显示,TNFα(3.83×10^(-10) mol/L作用3天)能抑制S期DNA合成。可见TNFα通过减少PTH受体数目以调节骨代谢。同时通过抑制DNA的合成以调节骨细胞的增殖。

Tumor Necrotic Factor alpha (TNF***********a), a 17kD protein secreted bystimulated monocytes, macrophages and osteoblastic cells, inhibit collagen synthesis in ROS 17/2.8 cells.In these studies, we examined the influence of TNF a on PTH receptor availability in post-confluent ROS 17/2.8 cells.Cells were treated with TNF***********a (from 3*******x 10-10 to 1*******x10-7 mol/L) for 4 days.Binding of 125I-[Nle8, Nle18, Tyr34] bPTH(1-34) amide decrease as a function of dose, and was directly related to duration of the exposure; maximal decrease in receptor binding occured within 3-4d.Scatchard analysis showed decreased available PTH binding sites from 5.23*********x105 to 3.6******x105 recptors per cell, without change in receptor affinity.In cell-cycle analysis, TNF ********a also inhibit DNA biosynthesis in S stage.These data suggest that TNF ********a has a local regulation in bone metabolism.