17-BETA-ESTRADIOL ACTS DIRECTLY ON THE CLONAL OSTEOBLASTIC CELL-LINE UMR106
17-BETA-ESTRADIOL ACTS DIRECTLY ON THE CLONAL OSTEOBLASTIC CELL-LINE UMR106
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DOI：
10.1073/pnas.84.17.6267
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发表时间：
1987-09-01
影响因子：
11.1
通讯作者：
NABELL, LM
中科院分区：
文献类型：
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作者：
GRAY, TK;FLYNN, TC;NABELL, LM
本文研究了17β-雌二醇(E)对克隆成骨细胞系UMR106细胞增殖和碱性磷酸酶活力的影响。在含E(10-8M)的培养液中孵育2d，细胞生长速度减慢，碱性磷酸酶活力升高。相反，E对人成纤维细胞系S90E的生长速度和碱性磷酸酶无影响。在细胞密度较低或融合时，未观察到E的作用。1，25-二羟基维生素D3可拮抗E的反应。用地塞米松(一种有效的分化诱导剂)预先孵育细胞，可逆转E或1，25-二羟基维生素D3的作用。这些结果表明，细胞和/或细胞外因素，如细胞密度，细胞周期的阶段，分化状态，以及是否有其他类固醇影响UMR106细胞对E的反应。血清被从培养上清液中去除，以最大限度地减少血清中存在的类固醇、生长因子和营养物质的影响。在无血清条件下，E对碱性磷酸酶有明显的刺激作用。在10~(-12)~10~(-8)M的浓度范围内，这种刺激是两相的，在10~(-10)M时反应最强。E对UMR106细胞的作用是代谢物特异性的，因为异构体17α-雌二醇对UMR106细胞的增殖率和碱性磷酸酶活力没有影响。这些细胞对甲状旁腺激素(残基1-34)的环AMP反应不受E处理的影响。相反，地塞米松暴露确实增加了对甲状旁腺激素的循环AMP反应。这些结果表明E对成骨细胞系有直接作用。他们还提出了在培养的正常成骨细胞中发生类似或相同的E作用的可能性。
We studied the effect of 17.beta.-estradiol (E) on the proliferation and alkaline phosphatase activity of cultured UMR106 cells, a clonal osteoblastic cell line. Growth rates were reduced and alkaline phosphatase activity was increased in cells incubated for 2 days in medium containing E (10-8 M). In contrast, E had no effect on the growth rates or alkaline phosphatase of a human fibroblastic cell line, S90E. The effect of E was not observed with low cell density or at confluence. 1,25-Dihydroxyvitamin D3 antagonized the response to E. Preincubation of the cells with dexamethasone, a potent inducer of differentiation, reversed the effect of E or 1,25-dihydroxyvitamin D3. These results indicate that cellular and/or extracellular factors such as cell density, the phase of the cell cycle, the state of differentiation, and the presence or absence of other steroids influenced the response of UMR106 cells to E. Serum was removed from the culture medium to minimize the effect of the steroids, growth factors, and nutrients present in serum. A striking stimulation of alkaline phosphatase by E occurred with serum-free conditions. This stimulation was biphasic over an E concentration from 10-12 to 10-8 M, with the peak response at 10-10 M. The action of E on UMR106 cells was metabolite-specific, since the isomer 17.alpha.-estradiol produced no effect on proliferation rates or alkaline phosphatase activity. The cyclic AMP response to parathyroid hormones (residues 1-34) was not altered by E treatment of these cells. In contrast, dexamethasone exposure did increase the cyclic AMP response to parathyroid hormone. These results demonstrate a direct effect of E on an osteoblastic cell line. They also raise the possibility that similar or identical actions of E occur in cultured normal osteoblasts.