Evidence for a role for insulin-like growth factor binding proteins in glucocorticoid inhibition of normal human osteoblast-like cell proliferation
Evidence for a role for insulin-like growth factor binding proteins in glucocorticoid inhibition of normal human osteoblast-like cell proliferation
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DOI：
10.1530/eje.0.1340591
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发表时间：
1996-05-01
影响因子：
5.8
通讯作者：
Linkhart, TA
中科院分区：
文献类型：
--
作者：
Chevalley, T;Strong, DD;Linkhart, TA
糖皮质激素（GC）在体内抑制骨形成，在体外抑制成骨细胞增殖和胶原合成。这些作用可能是由胰岛素样生长因子（IGF）系统的改变介导的。在目前的正常人成骨细胞样（HOB）细胞的研究中，我们测试了地塞米松（Dex）通过改变IGF结合蛋白（IGFBP）的表达，特别是通过降低IGFBP-5和IGFBP-3（增强IGF活性）的表达和增加IGFBP-4（抑制IGF作用）的表达来抑制骨中IGF合成代谢活性的假设。在7个独立的实验中，地塞米松处理引起HOB细胞增殖的剂量依赖性抑制（10（-8）mol/l Dex时为对照的69 +/-4%）。地塞米松（10（-8）和10（-7）mol/l）作用24 h，IGFBP-5 mRNA水平下降至对照组的20 - 30%。在6/6份HOB制剂中，10（-8）mol/l Dex降低IGFBP-5 mRNA水平（对照组的35 +/-7%），且该效应具有时间依赖性。地塞米松还降低IGFBP-3 mRNA水平（在三种HOB制剂中为对照的74 +/-9%）。地塞米松可减少29 - 31-kD IGFBP-5和38 - 42-kD IGFBP-3蛋白的分泌，通过Western配体印迹和IGFBP-5免疫印迹测定，并诱导剂量依赖性减少IGFBP-3和IGFBP-5分泌，通过特异性放射免疫测定测定。Dex对IGFBP-4 mRNA和25 kD IGFBP-4水平分泌的影响在不同细胞制剂之间不一致。结果表明，GC抑制IGFBP-5和IGFBP-3的产生可以降低IGF活性，并有助于GC抑制骨形成。
Glucocorticoids (GCs) inhibit bone formation in vivo and inhibit osteoblast proliferation and collagen synthesis in vitro. These effects may be mediated by alterations in the insulin-like growth factor (IGF) system. In the present study of normal human osteoblast-like (HOB) cells, we tested the hypothesis that dexamethasone (Dex) inhibits IGF anabolic activity in bone by altering expression of IGF binding proteins (IGFBPs), particularly by decreasing expression of IGFBP-5 and IGFBP-3 (which enhance IGF activity) and increasing expression of IGFBP-4 (which inhibits IGF actions). Dexamethasone treatment caused a dose-dependent inhibition of HOB cell proliferation (69 +/- 4% of control at 10(-8) mol/l Dex) in seven separate experiments. Dexamethasone decreased IGFBP-5 mRNA levels to 20-30% of control (10(-8) and 10(-7) mol/l for 24h). In six of six HOB preparations, 10(-8) mol/l Dex decreased IGFBP-5 mRNA levels (35 +/- 7% of control) and this effect was time dependent. Dexamethasone also decreased IGFBP-3 mRNA levels (74 +/- 9% of control in three HOB preparations). Dexamethasone decreased secretion of 29-31-kD IGFBP-5 and 38-42-kD IGFBP-3 proteins, determined by Western ligand blot and IGFBP-5 immunoblot, and induced a dose-dependent decrease in IGFBP-3 and IGFBP-5 secretion determined by specific radioimmunoassays. The effects of Dex on IGFBP-4 mRNA and on secretion of 25-kD IGFBP-4 levels were inconsistent between different cell preparations. Results suggest that GC inhibition of IGFBP-5 and IGFBP-3 production could decrease IGF activities and contribute to GC inhibition of bone formation.