Insulin-like growth factors sustain insulin-like growth factor-binding protein-5 expression in osteoblasts
Insulin-like growth factors sustain insulin-like growth factor-binding protein-5 expression in osteoblasts
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DOI：
10.1152/ajpendo.1998.275.2.e222
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发表时间：
1998-08-01
影响因子：
5.1
通讯作者：
Canalis, E
中科院分区：
文献类型：
--
作者：
Gabbitas, B;Canalis, E
胰岛素样生长因子（IGFs）I和II被认为是骨细胞功能的自分泌调节因子。最近，我们证明，IGF-I诱导IGF-结合蛋白-5（IGFBP-5）的表达在培养的成骨细胞富集细胞从22天胎鼠颅骨（Ob细胞）。在本研究中，我们假设，IC;Fs发挥自分泌的作用，在维持IGFBP-5的基础表达在Ob细胞。IGFBP-2和-3，在结合内源性IGF的浓度下，降低IGFBP-5 mRNA水平，如通过北方印迹分析所确定的，和蛋白质水平，如通过Ob细胞的细胞外基质提取物的Western免疫印迹所确定的。IGFBP-8和-3过量抑制IGFBP-5异质核RNA水平，通过RT-PCR测定，并没有改变转录停滞的Ob细胞中IGFBP-5 mRNA的半衰期。总之，阻断Ob细胞中的内源性IGFs抑制IGFBP-5的表达，表明IGFs是成骨细胞中IGFBP-5合成的自分泌诱导剂。
Insulin-like growth factors (IGFs)I and II are considered to be autocrine regulators of bone cell function. Recently, we demonstrated that IGF-I induces IGF-binding protein-5 (IGFBP-5) expression in cultures of osteoblast-enriched cells from 22-day fetal rat calvariae (Ob cells). In the present study, we postulated that IC;Fs play an autocrine role in the maintenance of IGFBP-5 basal expression in Ob cells. IGFBP-2 and -3, at concentrations that bind endogenous IGFs, decreased IGFBP-5 mRNA levels, as determined by Northern blot analysis, and protein levels, as determined by Western immunoblots of extracellular matrix extracts of Ob cells. IGFBP-8 and -3 in excess inhibited IGFBP-5 heterogeneous nuclear RNA levels, as determined by RT-PCR, and did not alter the half-life of IGFBP-5 mRNA in transcriptionally arrested Ob cells. In conclusion, blocking endogenous IGFs in Ob cells represses IGFBP-5 expression, suggesting that IGFs are autocrine inducers of IGFBP-5 synthesis in osteoblasts.