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人骨髓成骨基质细胞的体外分化:地塞米松诱导成骨细胞表型

Differentiation of human bone marrow osteogenic stromal cells in vitro: induction of the osteoblast phenotype by dexamethasone.

作者信息

Cheng S L, Yang J W, Rifas L, Zhang S F, Avioli L V

机构信息

Division of Bone and Mineral Diseases, Washington University School of Medicine, St. Louis, Missouri.

出版信息

Endocrinology. 1994 Jan;134(1):277-86. doi: 10.1210/endo.134.1.8275945.

DOI:10.1210/endo.134.1.8275945
PMID:8275945
Abstract

Human bone marrow stromal cells were examined for their osteogenic potential in an in vitro cell culture system. Dexamethasone (Dex) treatment induced morphological transformation of these cells from an elongated to a more cuboidal shape, increased their alkaline phosphatase activity and cAMP responses to PTH and prostaglandin E2, and was essential for mineralization of the extracellular matrix. Dex-induced differentiation of human bone marrow stromal cells was apparent after 2-3 days of treatment and reached a maximum at 7-14 days, as judged by alkaline phosphatase activity, although induction of osteocalcin by 1,25-dihydroxyvitamin D3 was attenuated by Dex. Withdrawal of Dex resulted in an enhancement of the 1,25-dihydroxyvitamin D3-induced secretion of osteocalcin, whereas alkaline phosphatase activity and the cAMP response to PTH remained at prewithdrawal levels. The steady state mRNA level of osteonectin was not affected by Dex. Our results, which demonstrate that Dex conditions the differentiation of human bone marrow osteogenic stromal cells into osteoblast-like cells, support the hypothesis of a permissive effect of glucocorticoids in ensuring an adequate supply of mature osteoblast populations. Furthermore, the established human bone marrow stromal cell culture provides a good model of an in vitro system to study the regulation of differentiation of human bone osteoprogenitor cells.

摘要

在体外细胞培养系统中检测人骨髓基质细胞的成骨潜能。地塞米松(Dex)处理诱导这些细胞从细长形态转变为更立方形,增加其碱性磷酸酶活性以及对甲状旁腺激素(PTH)和前列腺素E2的环磷酸腺苷(cAMP)反应,并且对细胞外基质矿化至关重要。根据碱性磷酸酶活性判断,Dex诱导人骨髓基质细胞分化在处理2 - 3天后明显,并在7 - 14天达到最大值,尽管1,25 - 二羟维生素D3诱导的骨钙素合成受到Dex的减弱。撤除Dex导致1,25 - 二羟维生素D3诱导的骨钙素分泌增强,而碱性磷酸酶活性以及对PTH的cAMP反应保持在撤除前水平。骨连接蛋白的稳态mRNA水平不受Dex影响。我们的结果表明Dex调节人骨髓成骨基质细胞向成骨样细胞的分化,支持糖皮质激素在确保充足成熟成骨细胞群体供应方面具有允许作用的假说。此外,已建立的人骨髓基质细胞培养为研究人骨祖细胞分化调控提供了一个良好的体外系统模型。

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