Effects of dioxin and estrogen on collagenase-3 in UMR 106-01 osteosarcoma cells.

Effects of dioxin and estrogen on collagenase-3 in UMR 106-01 osteosarcoma cells.
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二恶英和雌激素对 UMR 106-01 骨肉瘤细胞中胶原酶 3 的影响。

DOI:
10.1006/abbi.2000.1992
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发表时间:
2000
影响因子:
3.9
通讯作者:
Ruh,MF
Ruh,MF
中科院分区:
生物学3区
文献类型:
--
作者:
Partridge,NC;Fiacco,GJ;Walling,HW;Barmina,OY;Jeffrey,JJ;Ruh,MF

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由于雌激素在预防绝经后妇女骨质疏松症中的重要作用,而2,3,7,8-四氯二苯并-对-二恶英(TCDD)是生殖组织中的雌激素拮抗剂,因此,我们使用甲状旁腺激素(PTH)刺激的大鼠成骨细胞骨肉瘤细胞系UMR 106-01,研究了17β-雌二醇(E2)和TCDD对胶原酶-3分泌的影响。然而,在没有PTH的情况下,E2或TCDD对UMR细胞没有影响,在10− 7 M PTH存在下生长的细胞,其诱导胶原酶-3分泌急剧增加30倍,令人惊讶地证明了在TCDD或E2存在下进一步刺激胶原酶-3分泌。然而,增强反应是双相的;即,高浓度E2或TCDD对PTH的作用无增强作用。PTH对UMR细胞具有多种作用,包括诱导胶原酶-3 mRNA的转录,并通过特异性受体和内吞作用调节其胞外丰度。因此,我们使用北方分析来研究TCDD或E2刺激胶原酶-3 mRNA诱导的能力。如前所述,治疗4小时后,PTH剂量依赖性地诱导胶原酶-3 mRNA。TCDD或E2对PTH诱导的胶原酶-3 mRNA水平影响不大。这些数据不能解释对分泌型胶原酶-3的最终影响。我们推测,低浓度的E2和TCDD可能下调胶原酶-3内吞两步受体介导的过程,包括LDL受体相关蛋白,以增强PTH的作用。然而,事实并非如此。因此,我们得出结论,低浓度的TCDD和雌激素改变翻译或分泌的PTH刺激的胶原酶-3。
Since estrogen is important in preventing osteoporosis in postmenopausal women and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an estrogen antagonist in reproductive tissues, we investigated the effects of 17β-estradiol (E2) and TCDD on collagenase-3 secretion using parathyroid hormone (PTH)-stimulated UMR 106-01 cells, a rat osteoblastic osteosarcoma cell line. Whereas E2or TCDD had no effect on UMR cells in the absence of PTH, cells grown in the presence of 10−7M PTH, which induces a dramatic 30-fold increase in collagenase-3 secretion, surprisingly demonstrated a further stimulation of collagenase-3 secretion in the presence of TCDD or E2. However, the potentiating response was biphasic; i.e., at higher concentrations of E2or TCDD, there was no enhancement of the PTH effect. PTH induces multiple effects on UMR cells, including inducing collagenase-3 mRNA transcription and regulating its extracellular abundance through a specific receptor and endocytosis. Thus, we investigated the ability of TCDD or E2to stimulate the induction of collagenase-3 mRNA using Northern analysis. As previously reported, PTH dose dependently induced collagenase-3 mRNA after 4 h of treatment. There was little effect of TCDD or E2on PTH-induced levels of collagenase-3 mRNA. These data could not account for the final effects on secreted collagenase-3. We postulated that low concentrations of E2and TCDD may downregulate the collagenase-3 endocytotic two-step receptor-mediated process that includes the LDL-receptor-related protein to enhance the effects of PTH. However, this was not the case. Therefore, we conclude that low concentrations of TCDD and estrogen alter translation or secretion of PTH-stimulated collagenase-3.
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DOI: --
发表时间: 1993
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