Characterization of osteoblastic differentiation of stromal cell line ST2 that is induced by ascorbic acid

Characterization of osteoblastic differentiation of stromal cell line ST2 that is induced by ascorbic acid
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DOI:
10.1152/ajpcell.1999.277.1.c132
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发表时间:
1999-07-01
影响因子:
5.5
通讯作者:
Hagiwara, H
Hagiwara, H
中科院分区:
生物学2区
文献类型:
--
作者:
Otsuka, E;Yamaguchi, A;Hagiwara, H

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源自小鼠骨髓的基质细胞系 ST2 在抗坏血酸的作用下分化成成骨细胞样细胞。抗坏血酸诱导碱性磷酸酶 (ALPase) 活性、成骨细胞分化标志物蛋白质 mRNA 的表达、钙沉积以及 ST2 细胞矿化结节的形成。我们研究了抗坏血酸诱导ST2细胞分化的机制。胶原三螺旋形成的抑制剂完全阻断了抗坏血酸对ST2细胞的作用,这表明I型胶原的基质形成对于抗坏血酸诱导ST2细胞成骨细胞分化至关重要。我们进一步研究了骨形态发生蛋白(BMP)对抗坏血酸诱导的 ST2 细胞分化的影响。抗坏血酸对 BMP-4 和 BMP 受体的 mRNA 表达没有影响。然而,可溶形式的 BMP 受体 IA 抑制抗坏血酸诱导的 ALPase 活性。这些结果表明,抗坏血酸可能通过诱导 I 型胶原基质的形成,随后激活涉及 BMP 的信号通路,促进 ST2 细胞分化为成骨细胞样细胞。
The stromal cell line ST2, derived from mouse bone marrow differentiated into osteoblast-like cells in response to ascorbic acid. Ascorbic acid induced alkaline phosphatase (ALPase) activity, the expression of mRNAs for proteins that are markers of osteoblastic differentiation, the deposition of calcium, and the formation of mineralized nodules by ST2 cells. We investigated the mechanism whereby ascorbic acid induced the differentiation of ST2 cells. Inhibitors of the formation of collagen triple helices completely blocked the effects of ascorbic acid on ST2 cells, an indication that matrix formation by type I collagen is essential for the induction of osteoblastic differentiation of ST2 cells by ascorbic acid. We furthermore examined the effects of bone morphogenetic proteins (BMPs) on the differentiation of ST2 cells induced by ascorbic acid. Ascorbic acid had no effect on the expression of mRNAs for BMP-4 and the BMP receptors. However, a soluble form of BMP receptor IA inhibited the induction of ALPase activity by ascorbic acid. These results suggest that ascorbic acid might promote the differentiation of ST2 cells into osteoblast-like cells by inducing the formation of a matrix of type I collagen, with subsequent activation of the signaling pathways that involve BMPs.