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首页> 外文期刊>Rheumatology >High concentrations of dexamethasone suppress the proliferation but not the differentiation or further maturation of human osteoblast precursors in vitro: relevance to glucocorticoid-induced osteoporosis.
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High concentrations of dexamethasone suppress the proliferation but not the differentiation or further maturation of human osteoblast precursors in vitro: relevance to glucocorticoid-induced osteoporosis.

机译：高浓度的地塞米松在体外抑制人成骨细胞前体的增殖，但不能抑制其分化或进一步成熟：与糖皮质激素诱导的骨质疏松症有关。

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OBJECTIVE: The use of glucocorticoids (GCs) in the treatment of RA is a frequent cause of bone loss. In vitro, however, this same class of steroids has been shown to promote the recruitment and/or maturation of primitive osteogenic precursors present in the colony forming unit-fibroblastic (CFU-F) fraction of human bone and marrow. In an effort to reconcile these conflicting observations, we investigated the effects of the synthetic GC dexamethasone (Dx) on parameters of growth and osteogenic differentiation in cultures of bone marrow stromal cells derived from a large cohort of adult human donors (n=30). METHODS: Marrow suspensions were cultured in the absence and presence of Dx at concentrations between 10 pm and 1 microm. After 28 days we determined the number and diameter of colonies formed, the total number of cells, the surface expression of receptors for selected growth factors and extracellular matrix proteins and, based on the expression of the developmental markers alkaline phosphatase (AP) and the antigen recognized by the STRO-1 monoclonal antibody, the proportion of cells undergoing osteogenic differentiation and their extent of maturation. RESULTS: At a physiologically equivalent concentration, Dx had no effect on the adhesion of CFU-F or on their subsequent proliferation, but did promote their osteogenic differentiation and further maturation. These effects were independent of changes in the expression of the receptors for fibroblast growth factors, insulin-like growth factor 1, nerve growth factor, platelet-derived growth factors and parathyroid hormone/parathyroid hormone-related protein, but were associated with changes in the number of cells expressing the alpha(2) and alpha(4), but not beta(1), integrin subunits. At supraphysiological concentrations, the effects of Dx on the osteogenic recruitment and maturation of CFU-F and their progeny were maintained but at the expense of a decrease in cell number. CONCLUSIONS: A decrease in the proliferation of osteogenic precursors, but not in their differentiation or maturation, is likely to be a key factor in the genesis of GC-induced bone loss.
机译：目的：使用糖皮质激素（GCs）治疗RA是骨丢失的常见原因。然而，在体外，已经显示出同一类固醇可促进存在于人骨和骨髓的集落形成单位成纤维细胞（CFU-F）部分的原始成骨前体的募集和/或成熟。为了调和这些矛盾的意见，我们研究了合成GC地塞米松（Dx）对来自大量成年人类供体（n = 30）的骨髓基质细胞培养物中生长和成骨分化参数的影响。方法：在不存在和存在Dx的情况下，在10 pm和1微米之间的浓度下培养骨髓悬浮液。 28天后，我们根据形成标记碱性磷酸酶（AP）和抗原的表达，确定形成的菌落的数量和直径，细胞总数，选定生长因子和细胞外基质蛋白的受体的表面表达。被STRO-1单克隆抗体识别，经历成骨分化的细胞比例及其成熟程度。结果：在生理上相等的浓度下，Dx对CFU-F的粘附或随后的增殖没有影响，但确实促进了它们的成骨分化和进一步成熟。这些作用与成纤维细胞生长因子，胰岛素样生长因子1，神经生长因子，血小板衍生的生长因子和甲状旁腺激素/甲状旁腺激素相关蛋白受体表达的变化无关，但与甲状旁腺激素/甲状旁腺激素相关蛋白的改变有关。表达α（2）和α（4），但不表达β（1）整联蛋白亚基的细胞数量。在超生理浓度下，Dx对CFU-F及其后代的成骨细胞募集和成熟的影响得以维持，但以减少细胞数量为代价。结论：成骨前体增殖的减少，而不是其分化或成熟的减少，可能是GC诱导的骨丢失发生的关键因素。

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