Biphasic effects of leukemia inhibitory factor on osteoblastic differentiation *

Biphasic effects of leukemia inhibitory factor on osteoblastic differentiation *
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白血病抑制因子对成骨细胞分化的双相作用*

DOI:
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发表时间:
2001
期刊:
Journal of cellular biochemistry. Supplement
影响因子:
--
通讯作者:
J. Aubin
J. Aubin
中科院分区:
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文献类型:
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作者:
L. Malaval;J. Aubin

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白血病抑制因子(Leukemia inhibitory factor, LIF)是一种由包括成骨细胞在内的多种细胞类型产生的细胞因子,对骨代谢具有活性。我们之前已经证明,在骨结节形成的体外成骨模型中,胎鼠颅骨(RC)细胞模型,LIF抑制成骨细胞分化,作用于晚期成骨细胞和/或早期成骨细胞。这些结果与体内实验相反,在体内实验中发现LIF可以增加骨形成。为了解决这一差异,我们测试了LIF对大鼠骨髓(RBM)基质细胞培养的影响,这是一种包含早期骨祖细胞阶段的体外模型。在早期增殖的RBM培养中,LIF抑制细胞生长,但增加了培养的饱和密度。在该模型中,LIF对骨结节形成的影响是细胞密度依赖性和双相性的。连续用LIF处理可以减少融合、更成熟的培养物中存在的骨结节数量,并且当细胞密度较高时,抑制作用最强。相反,在RBM培养的早期阶段,LIF处理的培养皿中的结节数量高于对照组,并且在低密度培养皿中这种影响更大。限制在早期时间点的急性LIF治疗增加了成熟RBM细胞培养物中形成的骨结节的最终数量,但在RC细胞培养物中没有。我们的研究结果表明,在大鼠骨髓基质细胞模型中,LIF对骨祖细胞募集、分化和骨形成具有复杂的、阶段特异性的影响,并且这种影响是非细胞自主的。j .细胞。物化学。科学通报,2001,(3):63-70。©2001 Wiley‐Liss, Inc。
Leukemia inhibitory factor (LIF) is a cytokine produced by multiple cell types including osteoblasts and which is active on bone metabolism. We have previously shown that in a bone nodule forming in vitro model of osteogenesis, the fetal rat calvaria (RC) cell model, LIF inhibits osteoblast differentiation, acting on late osteoprogenitors and/or early osteoblasts. These results are in contrast to in vivo experiments, in which LIF has been found to increase bone formation. To resolve this discrepancy, we have tested the effect of LIF on rat bone marrow (RBM) stromal cell cultures, an in vitro model encompassing earlier osteoprogenitor stages. LIF inhibited cell growth in early, proliferating RBM cultures, but increased the culture saturation density. The effect of LIF on bone nodule formation in this model was cell density dependent and biphasic. Continuous treatment with LIF reduced the number of bone nodules present in confluent, more mature cultures, and the inhibitory effect was strongest when cells were plated at higher cell density than lower. In contrast, during the early stages of RBM culture, nodule numbers were higher in LIF‐treated dishes than in controls, and this effect was greater in lower density cultures. Acute LIF treatment restricted to early time points increased the final number of bone nodules formed in mature RBM cell cultures, but not in RC cell cultures. Our results indicate that LIF exerts complex, stage‐specific effects on osteoprogenitor recruitment, differentiation, and bone formation, and that the effects are cell nonautonomous, in the rat bone marrow stromal cell model. J. Cell. Biochem. Suppl. 36: 63–70, 2001. © 2001 Wiley‐Liss, Inc.
DOI: 10.1172/jci1039
发表时间: 1998-05-01
影响因子: 15.9
作者:
Jilka, RL;Takahashi, K;Manolagas, SC
通讯作者: Manolagas, SC