LEUKEMIA INHIBITORY FACTOR INHIBITS OSTEOGENIC DIFFERENTIATION IN RAT CALVARIA CELL-CULTURES
LEUKEMIA INHIBITORY FACTOR INHIBITS OSTEOGENIC DIFFERENTIATION IN RAT CALVARIA CELL-CULTURES
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DOI：
10.1210/en.136.4.1411
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发表时间：
1995-04-01
期刊：
影响因子：
4.8
通讯作者：
AUBIN, JE
中科院分区：
文献类型：
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作者：
MALAVAL, L;GUPTA, AK;AUBIN, JE
白血病抑制因子（LIF）是一种多效性细胞因子，对骨组织具有合成代谢和分解代谢作用。为了研究LIF对骨形成的影响，在没有再吸收周期的情况下，我们使用胎鼠颅骨细胞培养物和定量骨结节产生，其提供了一种集落测定来分析因素对骨祖细胞分化和骨形成的影响;在这些培养物中，地塞米松（Dex）刺激骨结节形成。在剂量-反应实验中，LIF抑制用（+Dex; ID 50 = 250 U/ml）或不用（-Dex; ID 50 = 30 U/ml）10（-8）M Dex培养的细胞的骨结节形成。残留的结核很小，矿化程度很低。连续暴露于LIF（500 U/ml）至第25天没有影响无论是生长速度或饱和密度的文化，但碱性磷酸酶活性和骨结节的生产，具有更大的抑制-地塞米松文化。在结节形成早期（约第10天）暴露于LIF（500 U/ml）3天可减少骨结节数量，其程度与-Dex培养物中的连续治疗相同，在+Dex培养物中显著，但不太明显;较早和较晚的脉冲没有影响。北方印迹分析在不同发育阶段的脉冲（-Dex）培养物中骨相关蛋白的信使RNA的表达，显示碱性磷酸酶、骨唾液蛋白和骨钙蛋白的显著抑制; I型胶原的轻微抑制;骨桥蛋白的早期刺激;对分泌蛋白、酸性和富含半胱氨酸/骨连接素没有影响。这些结果表明，LIF是在这些文化中的骨结节形成的抑制剂，在晚期骨祖细胞和/或早期成骨细胞存在的阶段起作用，并且Dex可以通过将有效剂量转移到更高浓度来调节LIF的作用。
Leukemia inhibitory factor (LIF) is a pleiotropic cytokine with both anabolic and catabolic effects on bone tissue. To investigate the effect of LIF on bone formation in the absence of a resorption cycle, we used fetal rat calvaria cell cultures and quantified bone nodule production, which provides a colony assay to analyze the effects of factors on osteoprogenitor differentiation and bone formation; In these cultures, dexamethasone (Dex) stimulates bone nodule formation. In dose-response experiments, LIF inhibited bone nodule formation by cells cultured with (+Dex; ID50 = 250 U/ml) or without (-Dex; ID50 = 30 U/ml) 10(-8) M Dex. Residual nodules were small and poorly mineralized. Continuous exposure to LIF (500 U/ml) up to day 25 did not affect either the growth rate or saturation density of the cultures, but decreased alkaline phosphatase activity and bone nodule production, with greater inhibition in -Dex cultures. Exposure to LIF (500 U/ml) for 3 days early during nodule formation (about day 10) reduced bone nodule numbers to the same extent as continuous treatment in -Dex cultures and significantly, but less markedly, in +Dex cultures; earlier and later pulses had no effect. Northern blot analysis of expression of messenger RNAs of bone related proteins in cultures pulsed (-Dex) at various stages of development showed marked inhibition of alkaline phosphatase, bone sialoprotein, and osteocalcin; slight inhibition of type I collagen; early stimulation of osteopontin; and no effect on Secreted Protein, Acidic and Rich in Cysteine/osteonectin. These results suggest that LIF is an inhibitor of bone nodule formation in these cultures, acting at a stage when late osteoprogenitors and/or early osteoblasts are present, and that Dex may modulate the effects of LIF by shifting effective doses to higher concentrations.