Regulation of insulin-like growth factors I and II and their binding proteins in human bone marrow stromal cells by dexamethasone
Regulation of insulin-like growth factors I and II and their binding proteins in human bone marrow stromal cells by dexamethasone
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DOI：
10.1002/(sici)1097-4644(19981201)71:3
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发表时间：
1998-12-01
影响因子：
4
通讯作者：
Avioli, LV
中科院分区：
文献类型：
--
作者：
Cheng, SL;Zhang, SF;Avioli, LV
糖皮质激素抑制骨髓基质细胞增殖，但诱导其向成骨样细胞分化。然而，这些机制仍然是非理性的。由于胰岛素样生长因子（IGFs）对成骨细胞的生长和分化具有深远的影响，糖皮质激素可能通过调节IGFs对骨髓基质细胞发挥作用。因此，我们分析了地塞米松（Dex）对培养的前成骨细胞正常人骨髓基质细胞（HBMSC）中IGF I和IGF II表达的影响。而Dex从治疗早期开始降低条件培养基中IGF I的浓度，IGF II的浓度随着培养时间的延长而逐渐增加。由于IGF I和IGF II的活性受IGF结合蛋白（IGFBPs）的调节，我们分析了Dex对IGFBPs表达的影响。地塞米松以时间依赖性方式增加IGFBP-2。然而，IGFBP-2的增加最多仅与IGF II的增加相同，这取决于治疗的时间长度。因此，IGFBP-2的增加会抑制，但不会消除IGF II活性的增加。相比之下，地塞米松降低IGFBP-3水平，后者增加IGF II的生物利用度。尽管Dex刺激IGFBP-4 mRNA水平，但条件培养基中的IGFBP-4浓度通过RIA测量不变。Dex可使IGFBP-5和IGFBP-6 mRNA水平呈时间依赖性降低。胰岛素样生长因子结合蛋白-5（IGFBP-5）在地塞米松治疗后1-4天也明显降低。HBMSC中未检测到IGFBP-1 mRNA。这些积累的数据表明，地塞米松调节IGF I和IGF II和它们的结合蛋白在正常人骨髓基质细胞的差异。IGF II的逐步增加可能有助于Dex诱导的细胞分化。J.细胞。71：449-458，1998中。(C)1998 Wiley-Liss，Inc.
Glucocorticoids inhibit the proliferation, but induce the differentiation, of bone marrow stromal cells into osteoblast-like cells. The mechanisms, however, are still conjectural. Since insulin-like growth factors (IGFs) have profound effects on osteoblast growth and differentiation, it is possible that glucocorticoids exert their effects on bone marrow stromal cells in part via regulation of IGFs. Therefore, we analyzed the effects of dexamethasone (Dex) on the expression of IGF I and IGF II in cultured preosteoblastic normal human bone marrow stromal cells (HBMSC). Whereas Dex decreased the concentration of IGF I in the conditioned medium since early in the treatment, the concentration of IGF II was increased progressively as culture period lengthened. As the activities of IGF I and IGF II are regulated by the IGF binding proteins (IGFBPs), we analyzed the effects of Dex on the expression of IGFBPs. Dex increased IGFBP-2 in a time-dependent manner. The increase in IGFBP-2, however, was only to the same extent as that of IGF II at most, depending on the length of treatment. Therefore, the increase in IGFBP-2 would dampen, but not eliminate, the increased IGF II activities. By contrast, Dex decreased IGFBP-3 levels, the latter increasing the bioavailability of IGF II. Although IGFBP-4 mRNA levels were stimulated by Dex, IGFBP-4 concentration in the conditioned medium was unchanged as measured by RIA. IGFBP-5 and IGFBP-6 mRNA levels were decreased by Dex in a time-dependent fashion. IGFBP-5 protein level was also decreased 1-4 days after Dex treatment. IGFBP-1 mRNA was not detectable in HBMSC. These accumulated data indicate that Dex regulates IGF I and IGF II and their binding proteins differentially in normal human bone marrow stromal cells. The progressive increase in IGF II may contribute to Dex-induced cell differentiation. J. Cell. Biochem. 71 :449-458, 1998. (C) 1998 Wiley-Liss, Inc.