肿瘤坏死因子-α对小鼠骨髓基质细胞护骨素表达的影响

Effects of tumor necrosis factor-alpha on expressions of osteoprotegerin mRNA and OPG protein in mouse marrow stromal MBA-1 cell lines

目的 探讨肿瘤坏死因子 -α(TNF- α)对骨髓基质细胞护骨素 (OPG)mRNA和蛋白质表达的影响以及TNF- α在骨代谢中的作用。方法 用TNF- α干预培养的小鼠骨髓基质MBA 1细胞 ,用RT PCR和Westernblot检测TNF- α不同剂量和不同作用时间时OPG表达变化。结果 ①MBA- 1细胞表达OPG ;②TNF -α对MBA- 1细胞OPGmRNA和OPG蛋白质表达有下调作用 ,但无剂量和时间依赖性 ;③ 17- β雌二醇 (17- βE2 )能阻断TNF α对MBA 1细胞OPG表达的下调作用 ;而吡咯二硫氨基甲酸酯 (PDTC ,一种核因子 κB抑制剂 )不能拮抗此作用。结论 TNF -α下调OPG表达。雌激素拮抗TNF- α,使MBA 1细胞OPG表达上调。TNF -α对OPG表达的影响与转录因子 - κB信息通路无关。

Objective To observe the effects of tumor necrosis factor-alpha (TNF-α) on the expressions of osteoprotegerin (OPG) in mouse bone marrow stromal MBA-1 cells, and investigate the potential roles of TNF-α in the pathogenesis of osteoporosis. Methods The expressions of OPG mRNA and OPG protein was assayed by RT-PCR and Western blot in BMA-1 cells treated with TNF-α in different concentrations and at different time-periods of cultures. Results (1) OPG was expressed in BMA-1 cell lines. (2) TNF-α downregulated the expression of OPG in BMA-1 cells in a dose-and time-independent manner. (3) 17β-estradiol suppressed the downregulation of TNF-α on the expression of OPG, whereas pyrrodine dithiocarbamete (PDTC) (inhibitor of nuclear factor-κB) had no effects on its downregulation. Conclusions TNF-α enhances osteoclastic bone resorption and bone loss by decreasing the expression of OPG in bone marrow stromal MBA-1 cells. The mechanism involved in the therapeutic effect of estrogen may associate with the suppression of OPG expression, but the signaling pathway that regulates OPG expression by TNF-α is not involved in the activation of nuclear fcator-κB.